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1.
We introduced previously an on-line resource, RANKPEP that uses position specific scoring matrices (PSSMs) or profiles for the prediction of peptide-MHC class I (MHCI) binding as a basis for CD8 T-cell epitope identification. Here, using PSSMs that are structurally consistent with the binding mode of MHC class II (MHCII) ligands, we have extended RANKPEP to prediction of peptide-MHCII binding and anticipation of CD4 T-cell epitopes. Currently, 88 and 50 different MHCI and MHCII molecules, respectively, can be targeted for peptide binding predictions in RANKPEP. Because appropriate processing of antigenic peptides must occur prior to major histocompatibility complex (MHC) binding, cleavage site prediction methods are important adjuncts for T-cell epitope discovery. Given that the C-terminus of most MHCI-restricted epitopes results from proteasomal cleavage, we have modeled the cleavage site from known MHCI-restricted epitopes using statistical language models. The RANKPEP server now determines whether the C-terminus of any predicted MHCI ligand may result from such proteasomal cleavage. Also implemented is a variability masking function. This feature focuses prediction on conserved rather than highly variable protein segments encoded by infectious genomes, thereby offering identification of invariant T-cell epitopes to thwart mutation as an immune evasion mechanism.  相似文献
2.
The BoLA (bovine lymphocyte antigen) Nomenclature Committee met during the 1994 and 1996 conferences of the International Society for Animal Genetics to define a sequence-based nomenclature system for genes of the BoLA system. The rules for acceptance of new sequences are described and names are assigned to the sequenced alleles of the class II genes DRA, DRB1, DRB2, DRB3, DQA, DQB, DYA, DIB, DMA and DMB . The assignment of BoLA class I sequences to loci will be considered at a later workshop when further sequencing/mapping data are available.  相似文献
3.
4.
Perspective: detecting adaptive molecular polymorphism: lessons from the MHC   总被引:13,自引:0,他引:13  
Abstract. In the 1960s, when population geneticists first began to collect data on the amount of genetic variation in natural populations, balancing selection was invoked as a possible explanation for how such high levels of molecular variation are maintained. However, the predictions of the neutral theory of molecular evolution have since become the standard by which cases of balancing selection may be inferred. Here we review the evidence for balancing selection acting on the major histocompatibility complex (MHC) of vertebrates, a genetic system that defies many of the predictions of neutrality. We apply many widely used tests of neutrality to MHC data as a benchmark for assessing the power of these tests. These tests can be categorized as detecting selection in the current generation, over the history of populations, or over the histories of species. We find that selection is not detectable in MHC datasets in every generation, population, or every evolutionary lineage. This suggests either that selection on the MHC is heterogeneous or that many of the current neutrality tests lack sufficient power to detect the selection consistently. Additionally, we identify a potential inference problem associated with several tests of neutrality. We demonstrate that the signals of selection may be generated in a relatively short period of microevolutionary time, yet these signals may take exceptionally long periods of time to be erased in the absence of selection. This is especially true for the neutrality test based on the ratio of nonsynonymous to synonymous substitutions. Inference of the nature of the selection events that create such signals should be approached with caution. However, a combination of tests on different time scales may overcome such problems.  相似文献
5.
MHC及其在种群遗传学和保护遗传学中的应用   总被引:13,自引:1,他引:12       下载免费PDF全文
杨光  陈旭衍  任文华  严洁 《遗传》2002,24(6):712-714
主要组织相容性复合体(major histocompatibility complex,MHC)是脊椎动物体内与免疫应答调节密切相关的一个基因家族,是基因组中多态性最丰富的区域。通过MHC的遗传变异分析可以提供物种的遗传多样性水平、进化历史和种群动态,以及种群遗传结构等信息,并在濒危物种饲养繁殖种群的遗传管理中有重要应用。 MHC and Its Application in the Population and Conservation Genetics YANG Guang,CHEN Xu-yan,REN Wen-hua,YAN Jie Institute of Genetic Resources,Nanjing Normal University,Nanjing 210097,China Abstract:The major histocompatibility complex (MHC),with the highest genetic polymorphism,is a cluster of genes involved in immune response regulation in the vertebrates.MHC can provide information such as population genetic diversity,evolutionary history and population dynamics,and population genetic structure etc.It can also be applied in the captive breeding programme for endangered vertebrate species. Key words:major histocompatibility complex (MHC);genetic diversity,population viability;population genetic structure;captive breeding  相似文献
6.
Heterozygosity-fitness correlations (HFCs) at noncoding genetic markers are commonly assumed to reflect fitness effects of heterozygosity at genomewide distributed genes in partially inbred populations. However, in populations with much linkage disequilibrium (LD), HFCs may arise also as a consequence of selection on fitness loci in the local chromosomal vicinity of the markers. Recent data suggest that relatively high levels of LD may prevail in many ecological situations. Consequently, LD may be an important factor, together with partial inbreeding, in causing HFCs in natural populations. In the present study, we evaluate whether LD can generate HFCs in a small and newly founded population of great reed warblers (Acrocephalus arundinaceus). For this purpose dyads of full siblings of which only one individual survived to adult age (i.e., returned to breed at the study area) were scored at 19 microsatellite loci, and at a gene region of hypothesized importance for survival, the major histocompatibility complex (MHC). By examining siblings, we controlled for variation in the inbreeding coefficient and thus excluded genome-wide fitness effects in our analyses. We found that recruited individuals had significantly higher multilocus heterozygosity (MLH), and mean d2 (a microsatellite-specific variable), than their nonrecruited siblings. There was a tendency for the survivors to have a more diverse MHC than the nonsurvivors. Single-locus analyses showed that the strength of the genotype-survival association was especially pronounced at four microsatellite loci. By using genotype data from the entire breeding population, we detected significant LD between five of 162 pairs of microsatellite loci after accounting for multiple tests. Our present finding of a significant within-family multilocus heterozygosity-survival association in a nonequilibrium population supports the view that LD generates HFCs in natural populations.  相似文献
7.
The biogenesis and functions of exosomes   总被引:9,自引:2,他引:7  
Exosomes are membrane vesicles with a diameter of 40–100 nm that are secreted by many cell types into the extracellular milieu. They correspond to the internal vesicles of an endosomal compartment, the multivesicular body and are released upon exocytic fusion of this organelle with the plasma membrane. Intracellularly, they are formed by inward budding of the endosomal membrane in a process that sequesters particular proteins and lipids. The unique composition of exosomes may confer specific functions on them upon secretion. Although their physiological role in vivo is far from being unraveled, it is apparent that they function in a multitude of processes, including intercellular communication during the immune response. Exosomes may have evolved early in the evolution of multicellular organisms and also seem to be important for tissue developmental processes.  相似文献
8.
  In both Old World and New World monkeys Mhc-DRB sequences have been found which resemble human DRB1*03 and DRB3 genes in their second exon. The resemblance is shared sequence motifs and clustering of the genes or the encoded proteins in phylogenetic trees. This similarity could be due to common ancestry, convergence at the molecular level, or chance. To test which of these three explanations applies, we sequenced segments of New World monkey and macaque genes which encompass the entire second exon and large parts of both flanking introns. The test strongly supports the monophyly of New World monkey DRB intron sequences. The phylogenies of introns 1 and 2 from DRB1*03-like and DRB3-like genes are congruent, but both are incongruent with the exon 2-based phylogeny. The matching of intron 1- and intron 2-based phylogenies with each other suggests that reciprocal recombination has not played a major role in exon 2 evolution. Statistical comparisons of exon 2 from different DRB1*03 and DRB3 lineages indicate that it was neither gene conversion (descent), nor chance, but molecular convergence that has shaped their characteristic motifs. The demonstration of convergence in anthropoid Mhc-DRB genes has implications for the classification, age, and mechanism of generation of DRB allelic lineages. Received: 30 August 1999 / Revised: 19 October 1999  相似文献
9.
奶牛MHC基因多态性及其与经济性状关系的研究进展   总被引:7,自引:0,他引:7       下载免费PDF全文
叶素成  储明星  陈国宏 《遗传》2003,25(1):89-92
本文简述了奶牛 MHC基因的结构、位置、分类、多态性的一般特性,并且介绍了 MHC基因与生产性状、乳房炎等一些经济性状的关系。  相似文献
10.
Previous research indicates that the scent of developmentalstability (low fluctuating asymmetry, FA) is attractive to womenwho are fertile (at high-conception risk points in their menstrualcycles), but not to other women or men. Prior research alsoindicates that the scent of dissimilarity in major histocompatibilitycomplex (MHC) genes may play a role in human mate choice. Westudied the scent attractiveness to the opposite sex of t-shirtsworn for 2 nights' sleep. Our results indicate that the twoolfactory systems are independent. We repeated previous resultsfrom studies of the scent of symmetry. We repeated previousresults from MHC research in part; men, but not women, showeda preference for t-shirts with the scent of MHC dissimilarity.Women's scent ratings of t-shirts were uncorrelated with thewearer's MHC dissimilarity and allele frequency, but positivelycorrelated with the wearer's MHC heterozygosity. Fertile womendid not exhibit any MHC trait preferences. Women's preferencefor the scent of men who were heterozygous for MHC alleles maybe stronger in women who are at infertile cycle points. Menpreferred the scent of common MHC alleles, which may functionto avoid mates with rare alleles that exhibit gestational drive.Men also preferred the scent of women at fertile cycle points.The scent of facially attractive women, but not men, was preferred.Neither FA nor facial attractiveness in either sex correlatedwith MHC dissimilarity to others, MHC heterozygosity, or MHCallelic rarity.  相似文献
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