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生物学基本名词详细解释(中英文对照)/english/speciality/5091.html组织相容性 Histocompatibility字面上讲是指不同组织共存的能力;严格地讲是指所有移植蛋白的一致性,这是阻止移植和器官排斥的需要。组织相容性的分子基础是修饰几乎所有人类细胞表面的一套移植蛋白。这些蛋白是由位于6号染色体上的一段称为主要组织相溶性复合体基因,MHC编码的。这些蛋白高度多态。例如,它们在不同的人中显示差异。尽管很多人会有一些相同的MHC分子,极少数人有完全相同的MHC分子。微小的差别导致这些蛋白质被移植受体的免疫系统识别为外来的而进行破坏。对成功的移植来说这些蛋白质应该在供体和受体之间相匹配。双胞胎相配的几率最高,接下来是兄弟姐妹。在一般人群中只有10万分之一的比例是MHC匹配的,可以允许移植。 Literally, the ability of different tissues to “get along”; strictly, identity in all of the transplantation proteins, which is a requirement for the prevention of graft or organ rejection. The molecular basis of histocompatibility is a set of transplantation proteins that decorate the surface of nearly all human cells. These proteins are encoded by genes that are grouped on a part of chromosome 6 called the major histocompatibility complex, or MHC. These proteins are highly “polymorphic” i.e., they show variation in different individuals. Although many individuals may share some identical MHC molecules, a very low number share all the MHC molecules. The consequence of these minor differences is that these proteins are recognized by the transplant recipients immune system as being foreign, and so are targeted for destruction (since the immune systems job is to eradicate any foreign proteins or cells that invade the body). For successful transplantation these proteins ideally should be matched between donor and recipient. Twins have the highest rate of match, followed by siblings. In the general population only 1 in 100,000 individuals is sufficiently “MHC matched” to another person to allow transplantation. X射线结晶学 X-ray Crystallography阐述蛋白质、DNA或其它生物分子的原子水平的三维结构的技术。这种方法的运用是基于首先使纯化的生物分子结晶为有序排列然后用X射线分析结晶体。之所以使用X射线是因为其波长和原子裂解时的波长一样,所以晶体作为分子衍射光栅衍射X射线,产生一种可以获取并分析的衍射图形。然后用计算机重建初始结构。在实际操作中这一衍射图形被反复地不断升高的分辨率处理,结晶学家不断在建立一个模型结构并按该模型计算出的衍射图形与实际观察到的比较。每一次重复都使模型结构与实验结果更加吻合。当这两者之间的差异可以忽略时,这一衍射图形便得到求解。最终的模型提供了被研究分子平均时间上的三维原子水平结构。蛋白靶子的X射线结晶体结构可以识别蛋白质的功能袋。当与自然或人工配体混合时,可以作为药物设计的有用起始点。蛋白质X射线结构的目录也为蛋白质结构类型、自然状态下的折叠和域提供了有用信息。有时这被称为结构基因组学。 A technique that allows the elucidation of the three-dimensional structure of proteins, DNA, or other biomolecules at atomic-level resolution. This is achieved by first crystallizing the purified biomolecule into ordered arrays and then using X-ray diffraction to analyze the crystals. X-rays are used because they have the same wavelength as the atomic separations so the crystal acts as a molecular diffraction grating to diffract a beam of X-rays, producing a diffraction pattern that can be captured and analyzed. A computer is then used to reconstruct the original structure. In practice the diffraction pattern is iteratively solved at ever-increasing “shells” of resolution; the crystallographer alternates between building a model structure (working in “real” space) and comparing the models calculated diffraction pattern with the observed diffraction pattern (working in “reciprocal” space). Each round of iteration brings the model structure into better agreement with the experimental data; when the difference between the two is negligible the diffraction pattern is said to be “solved.” The final model provides a time-averaged three-dimensional atomic-resolution structure of the molecule under study. The X-ray crystal structure of a protein target can identify the functional pockets of the protein and, when complexed with a natural or synthetic ligand, can serve as a useful starting point for rational drug design. X-ray structures of catalogs of proteins have also provided useful information on the types of protein structures, folds and domains found in nature; this is sometimes termed structural genomics. 药效基因 Pharmacophore一个药物分子经过物理或电场作用形成三维功能结构从而引起分子的药理活动。一般而言,药效基因是指原子和功能基团的结合,使得药物以特定方式与靶蛋白作用并显示药物活性。人们已经发展了很多研究药物先导物和其针对特定靶子的可测量活性的方法,使得研究者能够从一系列结构活性关系中得到其药效基因。这些方法中最成熟的是用复杂的统计计算机模型和三维数据库查询,识别和设计具有相近或相同药效基因的复合物或整个文库。药效基因的识别不仅在药物识别和设计中有用,而且对先导物优化药效减少毒性也大有用途。这是因为一旦知道药效基因,药物化学家就可以修饰它,在保持药效的基础上减少毒性。 The three-dimensional “functional shape” formed by the steric (physical) and electric fields of a drug molecule that cause the molecules pharmacological activity. Typically, pharmacophore refers to the combination of atoms and functional groups (together with their three-dimensional positions), that together allow a drug to interact with its target protein in a specific manner and exhibit its pharmacological activity. Numerous approaches for studying drug leads and their measurable activity against a particular target have been developed, allowing one to infer the pharmacophore from a series of these structure-activity relationships. The most sophisticated of these approaches use sophisticated statistical computer modeling and three-dimensional database searching to identify and design compounds or entire libraries with similar or identical pharmacophores. Identification of a pharmacophore is useful not only in drug identification and design studies, but also in lead optimization (see leads) for potency and reduction of toxicity. This is because once a pharmacophore is known, medicinal chemists can modify it to reduce toxicity while maintaining (or enhancing) potency. 异种移植 Xenograft将一个物种的组织移植到另一个物种体内,例如,从猪到人。和同种移植不同的是,异种之间存在很大差异,从而使得这种移植成功的可能性很小。负责组织排斥的免役系统将很容易地识别出外来组织并强烈排斥它。既然动物可以为移植提供无尽的来源,异种移植一直是人们梦寐以求的事。猪虽然看上去和人有着很大的差异,却有着相似的器官结构,因而成为该领域内研究的焦点;猴子是另一类有吸引力的种群。 A tissue transplant from one species to another, e.g. from pig to human. Because of the greater differences between species, as opposed to within a species, these transplants have the least chance of working. The immune system, which is responsible for tissue rejection, will easily recognize the tissue as foreign and will reject it vigorously. Thus xenograft, or xenotransplantation is a sort of holy grail for transplantation, since animals would provide an endless supply of organs for transplantation. Pigs, although seemingly very different from humans, have similar organ organization and so remain a focus for research in this area; monkeys are another attractive group. 大规模筛选 High-throughput Screening用小型的、自动机技术针对靶蛋白、细胞或组织筛选大量化合物文库以识别潜在新药。结合基因组学和组合化学,大规模筛选为药物和生物技术公司识别潜在新药的能力带来了革命。大规模筛选有赖于对要识别的靶子的数量和药物相关分析的发展,然后可以在大量样本中重复。一般,大规模筛选依赖于96孔板,尽管更高密度的形式也是可能的。最近,小型化和微流体方面的进展允许在一个芯片上每天对一个靶子筛选10万个化合物,使得从前不可想象的大量化合物筛选成为可能。 The use of miniaturized, robotics-based technology to screen large compound libraries against an isolated target protein, cell or tissue in order to identify binders that may be potential new drugs. In conjunction with genomics (the identification of large numbers of potential therapeutic targets), and combinatorial chemistry (the production of large numbers of medicinally relevant compounds), high-throughput screening has revolutionized the capacity of pharmaceutical and biotechnology companies to identify potential new drugs. High-throughput screening depends on the development of a quantitative, pharmacologically relevant assay for the identified target, which can then be reproduced across a large number of samples. Typically, high-throughput screening has relied on 96-well plates as the standard, although higher-density formats (356, 712) are possible. Recently, advances in miniaturization and microfluidics have allowed screening of up to 100,000 compounds against a target on a single chip daily, allowing previously unimaginable amounts of compounds to be screened.药物遗传学 Pharmacogenomics药物遗传学是基于人群的遗传变异研究该人群对药物的遗传反应的分别。人们早已知道人群里的不同人对同一种药物的反应不同,这是受药物影响的分子受体的不同或清除药物的代谢酶的差异造成的。药物遗传学是在分子水平上研究这些差异的科学。通过对人群中存在的不同的分子受体进行识别和分类,然后系统研究药物对其影响,人们有希望预测或抑制药物对不同亚人群的作用。药物遗传学的应用包括减少副作用,定制药物,改善临床实验以及挽救一些由于对少数人群会产生严重副作用而被禁用的药物。 Pharmacogenomics is the study of the stratification of the pharmacological response to a drug by a population based on the genetic variation of that population. It has long been known that different individuals in a population respond to the same drug differently, and that these variations are be due to variations in the molecular receptors being affected by the drug, or to differences in metabolic enzymes that clear the drug. Pharmacogenomics is the science of studying these variations at the molecular level. By identifying and classifying all the tolerable variations of a molecular receptor known to exist in a population, and then performing systematic studies of the effect of the drug on each of the variants, one can hope to predict or constrain the use of the drug to different subgroups. Applications of pharmacogenomics include reducing side effects; customized drugs; improved clinical trials; and the rescue of some drugs that have been banned due to severe side effects in a small percentage of the eligible population. 基因治疗 Gene Therapy用基因材料进行治疗的技术。这种基因材料可以是基因,基因替代物或cDNA、RNA甚至小的基因片段。引入的遗传材料可以在几方面有治疗作用:它可以合成一个蛋白质替代缺陷或遗失蛋白,或修正和修饰一项特定的细胞功能,或引发免疫反应。在基因治疗方法中,基因材料可以以多种方式引入病人体内。它可以以基因疫苗的方式注射,或者将携带治疗基因作为其原有基因的一部分的生物工程病毒引入体内。使用的病毒可以是腺病毒、AAV、反转录病毒、疱疹病毒。脂质体也可携带治疗基因到细胞内。 The technology that uses genetic material for therapeutic purposes. This genetic material can be in the form of a gene, a representative of a gene or cDNA, RNA or even a small fragment of a gene. The introduced genetic material can be therapeutic in several ways: It can make a protein that is defective or missing in the patients cells (as would be the case for a genetic disorder), or one which will correct or modify a particular cellular function, or a protein that elicits an immune response. In gene therapy approaches, the genetic material may be introduced into the patient in several different ways. It can be directly injected for some applications in a process known as genetic vaccination, or it can be introduced by using bioengineered viruses that will carry the therapeutic gene as part of their own genetic cargo and deliver it into the cell. The viruses that are commonly used for this purpose are adenovirus, adeno-associated virus (AAV), retrovirus, lentivirus and herpes virus. Reagents known as liposomes can also carry therapeutic genes into cells.载体 Vector把物质(一般是遗传物质)转入宿主细胞或生物的运载体。一般而言,载体有两种类型-病毒或DNA类。DNA载体是可以自我复制的环状结构,易于携带遗传物质和纯化。用一般的实验室技术将它们转入细胞体内。这些载体具有不同的特征,包括质粒、粘粒和酵母人工染色体。经过生物工程处理成无害的组合病毒也可携带遗传物质并在实验室内将其转入细胞或整个宿主生物体,后者即基因治疗的一个例子。 A vehicle that transfers material (typically genetic) into a host cell or organism. Typically, vectors are of two types viral- or DNA-based. DNA vectors are self replicating, circular elements that can be easily manipulated to carry genetic cargo and are easily purified in bulk; they are transferred into cells by standard laboratory techniques. These vectors can have different features (such as the size of DNA-insert they can accommodate) and include plasmids, cosmids, and yeast artificial chromosomes (YACs). Recombinant viruses that have been bioengineered to be harmless can also carry genetic cargo for transfer into cells in the laboratory, or into an entire host organism, the latter is an example of gene therapy.多聚酶链式反应(PCR)Polymerase Chain Reaction (PCR)扩大DNA量的技术,其中目标DNA的两侧序列是知道的。短的DNA片段(引物)通过特殊的TAQ酶结合在侧翼序列上并在两个引物间复制序列。循环升温分离DNA双链,降温使引物结合,再升温使酶能复制DNA。这样每一循环产生双倍DNA。这一反应通常是在一可调控的温箱中或PCR仪中进行,对所有的DNA进行30到35个循环扩增。PCR十分敏感,可以从一个DNA分子扩增到微克的量。靶子DNA可以是任何来源,所以用PCR来扩增DNA的方法可以用于研究,克隆和司法签定,它们都可以利用PCR的极度敏感性。 A technique used to “amplify” (or generate large amounts) of DNA for which the “flanking” sequences (those sequences directly on either side of the target DNA) are known. Short complementary DNA fragments (“primers”), which bind these flanking sequences are used by a special enzyme (Taq polymerase which is active at high temperatures) to copy the sequence in-between the primers. Cycles of heat to break apart the DNA strands, cooling to allow the primers to bind, and heating again to allow the enzyme to copy the intervening sequence, lead to a doubling of DNA at each cycle. The reactions are typically carried out on a regulated heating block, or PCR machine, and consist of 30-35 cycles of repeated amplification of all the DNA present. PCR is very sensitive, allowing a single molecule of target DNA to be amplified to microgram amounts of DNA. The target DNA can be of any origin, and so PCR is used to amplify DNA for use in research, cloning and forensics, each of which takes advantage of PCRs extreme sensitivity 基因 Gene是构成遗传的基本单位;编码蛋白所有信息的DNA序列。从结构上来讲,基因包含三个区域:称为启动子的调节区域;与其并列的编码蛋白质的密码子区域;以及3端尾部序列。在哺乳动物细胞里,启动子是一个包含着许多蛋白质结合位点的复杂区域,它调节基因的表达。单个基因可以被激活,由这些控制蛋白决定时间、地点及蛋白表达量,从而产生蛋白质。这一过程称为基因表达。在人类基因组中,大约有10万个基因。其中一些进化过程相关联而形成 基因家族表达相关蛋白。也有基因不再制造蛋白,这些进化中的残余物称为假基因。 The basic unit of heredity; the sequence of DNA that encodes all the information to make a protein. Structurally, a gene is formed by three regions: a regulatory region called the promoter juxtaposed to the coding region containing the protein sequence, and a “3 tail” sequence. In mammalian cells, the promoter is a complex region containing binding sites for many proteins that regulate gene expression. A gene may be “activated” or “switched on” to make protein this activation is referred to as gene expression - by these proteins which control when, where and how much protein is expressed from the gene. In the human genome, there are an estimated 100,000 genes. Some of these are evolutionarily related and form“gene families” that express related proteins. There are also genes that no longer make a protein; these defective remnants of evolution are called pseudogenes. 疫苗 Vaccines由无害的多种致病介质如病毒或细菌或来自这些介质的蛋白质组成的生物制品。当注入人体时,介质本身或其蛋白质亚基会引发很强的免疫反应从而避免对同种介质的进一步感染。疫苗模仿自然的感染引发强大的免疫反应而不会造成疾病。疫苗中使用的蛋白质通常在致病介质表面找到并可以在实验室生成。完整的细菌或病毒可以通过热和辐射处理变得无害,也可以通过生物处理使其活性减弱变成活的无害的介质。这样的例子包括不能在体温下生长的流感病毒和在病人体内不能感染神经的小儿麻痹症疫苗。 Biological preparations composed either of a harmless variety of a disease-causing agent such as a virus or bacteria, or of proteins derived from such an agent. When injected into humans, the agent itself or its protein subunits, will elicit a strong immune response, which will be protective against further infection from that agent. The vaccine “mimics” a natural infection to elicit a strong immune response, but causes no disease. The proteins used in vaccines are usually found on the surface of the disease-causing agents and can be generated in the laboratory. Intact bacteria or viruses can be rendered harmless by heat- or radiation- mediated killing, or can be “attenuated” (inactivated) by biomanipulation to produce a live but harmless version of the agent. Examples of such “attenuated” or “live vaccines” include influenza virus that does not grow at body temperature and polio vaccine in which the virus cannot infect neurons but remains in the gut of the patient. 病原体 Pathogen任何对身体有害的外来物或生物。一般来说,病原体是微生物,如:细菌、病毒、真菌或寄生虫。每一种情况中,感染生物都用寄主的身体来生存和生长,经常集中于一个特定器官。有时这会影响正常的细胞功能导致疾病。有些细菌还会分泌对寄主有毒的蛋白质导致轻度反应如腹泻,重则会致命。病原体展现出一系列特殊的蛋白质,允许它们感染寄主并在其体内生长;这些蛋白质是治疗的靶子。 Any foreign agent or organism that is harmful to the body. Typically, pathogens are microscopic organisms such as bacteria, viruses, fungi or parasites such as worms. In each case, the infecting organism uses the host body to live and grow, and is often restricted to a particular organ. Sometimes this affects normal cellular functions, leading to illness. Some bacteria also secrete proteins that are toxic for the host, leading to mild effects such as diarrhea, or to fatal effects. Pathogens exhibit a unique set of proteins, which allow them to infect and grow in their hosts; these proteins are the target of therapeutic intervention. 功能基因组学 Functional Genomics运用遗传技术,通过识别其在一个或多个生物模型中的作用来认识新发现基因的功能。功能基因组用功能不明的分离基因作为起始点,然后选择具有该同源基因的生物模型。这一生物模型可以是简单的酵母细胞或复杂的线虫甚至老鼠。基因被选择性的用多种遗传技术灭活,在此生物体上选择性去除的效果被确定。通过这种方法去除基因,它对生物功能的贡献就能够被识别。功能基因组在评估和检测新药时十分有用。在另一种方法中,一整套基因被系统地灭活,人们就可以检测其对特定细胞功能的影响。这里,一个新的基因和其功能就同时被识别了。 The use of genetic technology to determine the function of newly discovered genes by determining their role in one or more model organisms. Functional genomics uses as its starting point the isolated gene whose function is to be determined, and then selects a model organism in which a homolog of that gene exists. This model organism can be as simple as a yeast cell or as complex as a nematode worm, fruitfly, or even a mouse. The gene is selectively inactivated or knocked out using a variety of genetic techniques, and the effect of its selective deletion on that organism is determined. By knocking out a gene in this way, its contribution to the function of the organism (and, by implication, its function in man), can be determined. Functional genomics has proven particularly useful as a means of validating or testing novel therapeutic targets. In another approach, a whole set of genes may be systematically inactivated and the effect of this on a particular cellular function examined. Here, a new gene and its function are identified simultaneously. 翻译 Translation细胞的蛋白质合成系统将mRNA的信息转化成蛋白质中的过程。翻译发生于核糖体上,在那里将mRNA的信息转变为多肽链。一系列转移RNA分子将每三个碱基读成一个密码子,识别出mRNA的信息并将氨基酸相应排列起来。并列而排的转移RNA阅读邻近的密码子,带来氨基酸并将其以共价键连接起来。这一过程持续进行直到多肽链完成;这条链然后被释放出来并折叠成有功能的蛋白质。 The conversion of an mRNA transcript (see transcription) into a protein molecule by the cellular protein synthesis machinery. Translation occurs at a site called the ribosome, which allows the information within the mRNA to be converted into a polypeptide chain. The code is read, three bases at a time, by a series of transfer RNA (tRNA) molecules, which recognize the mRNA message and align the appropriate amino acid in place. Juxtaposed tRNAs, reading adjacent codes, bring together amino acids, which are then covalently joined to together. This process continues until the polypeptide chain is complete; the chain is then released and folds into a functional protein. 开放阅读框(ORF)Open reading frame放阅读框是基因序列的一部分,包含一段可以编码蛋白的碱基序列,不能被终止子打断。当一个新基因被识别,其DNA序列被解读,人们仍旧无法搞清相应的蛋白序列是什麽。这是因为在没有其它信息的前提下,DNA序列可以按六种框架阅读和翻译(每条链三种,对应三种不同的起始密码子)。ORF识别包括检测这六个阅读框架并决定哪一个包含以启动子和终止子为界限的DNA序列而其内部不包含启动子或密码子,符合这些条件的序列有可能对应一个真正的单一的基因产物。ORF的识别是证明一个新的DNA序列为特定的蛋白质编码基因的部分或全部的先决条件。 An open reading frame (O

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