全文获取类型
收费全文 | 1053篇 |
免费 | 2篇 |
国内免费 | 3篇 |
专业分类
系统科学 | 13篇 |
教育与普及 | 5篇 |
理论与方法论 | 8篇 |
现状及发展 | 235篇 |
研究方法 | 164篇 |
综合类 | 614篇 |
自然研究 | 19篇 |
出版年
2021年 | 3篇 |
2018年 | 5篇 |
2017年 | 8篇 |
2016年 | 17篇 |
2015年 | 11篇 |
2014年 | 18篇 |
2013年 | 14篇 |
2012年 | 73篇 |
2011年 | 108篇 |
2010年 | 31篇 |
2009年 | 8篇 |
2008年 | 71篇 |
2007年 | 71篇 |
2006年 | 62篇 |
2005年 | 72篇 |
2004年 | 56篇 |
2003年 | 61篇 |
2002年 | 71篇 |
2001年 | 12篇 |
2000年 | 17篇 |
1999年 | 17篇 |
1998年 | 4篇 |
1996年 | 3篇 |
1994年 | 4篇 |
1992年 | 6篇 |
1991年 | 7篇 |
1990年 | 6篇 |
1989年 | 8篇 |
1988年 | 4篇 |
1987年 | 7篇 |
1986年 | 8篇 |
1985年 | 6篇 |
1983年 | 4篇 |
1982年 | 4篇 |
1980年 | 2篇 |
1979年 | 12篇 |
1978年 | 13篇 |
1977年 | 11篇 |
1976年 | 6篇 |
1975年 | 7篇 |
1974年 | 9篇 |
1973年 | 11篇 |
1972年 | 8篇 |
1971年 | 14篇 |
1970年 | 18篇 |
1969年 | 15篇 |
1968年 | 8篇 |
1967年 | 18篇 |
1966年 | 8篇 |
1965年 | 5篇 |
排序方式: 共有1058条查询结果,搜索用时 15 毫秒
91.
92.
93.
Genetic analysis of the mouse brain proteome 总被引:24,自引:0,他引:24
Klose J Nock C Herrmann M Stühler K Marcus K Blüggel M Krause E Schalkwyk LC Rastan S Brown SD Büssow K Himmelbauer H Lehrach H 《Nature genetics》2002,30(4):385-393
Proteome analysis is a fundamental step in systematic functional genomics. Here we have resolved 8,767 proteins from the mouse brain proteome by large-gel two-dimensional electrophoresis. We detected 1,324 polymorphic proteins from the European collaborative interspecific backcross. Of these, we mapped 665 proteins genetically and identified 466 proteins by mass spectrometry. Qualitatively polymorphic proteins, to 96%, reflect changes in conformation and/or mass. Quantitatively polymorphic proteins show a high frequency (73%) of allele-specific transmission in codominant heterozygotes. Variations in protein isoforms and protein quantity often mapped to chromosomal positions different from that of the structural gene, indicating that single proteins may act as polygenic traits. Genetic analysis of proteomes may detect the types of polymorphism that are most relevant in disease-association studies. 相似文献
94.
95.
The knowledge of human genetic variation that will come from the human genome sequence makes feasible a polygenic approach to disease prevention, in which it will be possible to identify individuals as susceptible by their genotype profile and to prevent disease by targeting interventions to those at risk. There is doubt, however, regarding the magnitude of these genetic effects and thus the potential to apply them to either individuals or populations. We have therefore examined the potential for prediction of risk based on common genetic variation using data from a population-based series of individuals with breast cancer. The data are compatible with a log-normal distribution of genetic risk in the population that is sufficiently wide to provide useful discrimination of high- and low-risk groups. Assuming all of the susceptibility genes could be identified, the half of the population at highest risk would account for 88% of all affected individuals. By contrast, if currently identified risk factors for breast cancer were used to stratify the population, the half of the population at highest risk would account for only 62% of all cases. These results suggest that the construction and use of genetic-risk profiles may provide significant improvements in the efficacy of population-based programs of intervention for cancers and other diseases. 相似文献
96.
97.
Martin N Jaubert J Gounon P Salido E Haase G Szatanik M Guénet JL 《Nature genetics》2002,32(3):443-447
Mice that are homozygous with respect to the progressive motor neuronopathy (pmn) mutation (chromosome 13) develop a progressive caudio-cranial degeneration of their motor axons from the age of two weeks and die four to six weeks after birth. The mutation is fully penetrant, and expressivity does not depend on the genetic background. Based on its pathological features, the pmn mutation has been considered an excellent model for the autosomal recessive proximal childhood form of spinal muscular atrophy (SMA). Previously, we demonstrated that the genes responsible for these disorders were not orthologous. Here, we identify the pmn mutation as resulting in a Trp524Gly substitution at the last residue of the tubulin-specific chaperone e (Tbce) protein that leads to decreased protein stability. Electron microscopy of the sciatic and phrenic nerves of affected mice showed a reduced number of microtubules, probably due to defective stabilization. Transgenic complementation with a wildtype Tbce cDNA restored a normal phenotype in mutant mice. Our observations indicate that Tbce is critical for the maintenance of microtubules in mouse motor axons, and suggest that altered function of tubulin cofactors might be implicated in human motor neuron diseases. 相似文献
98.
Activation-induced cytidine deaminase turns on somatic hypermutation in hybridomas 总被引:19,自引:0,他引:19
The production of high-affinity protective antibodies requires somatic hypermutation (SHM) of the antibody variable (V)-region genes. SHM is characterized by a high frequency of point mutations that occur only during the centroblast stage of B-cell differentiation. Activation-induced cytidine deaminase (AID), which is expressed specifically in germinal-centre centroblasts, is required for this process, but its exact role is unknown. Here we show that AID is required for SHM in the centroblast-like Ramos cells, and that expression of AID is sufficient to induce SHM in hybridoma cells, which represent a later stage of B-cell differentiation that does not normally undergo SHM. In one hybridoma, mutations were exclusively in G*C base pairs that were mostly within RGYW or WRCY motifs, suggesting that AID has primary responsibility for mutations at these nucleotides. The activation of SHM in hybridomas indicates that AID does not require other centroblast-specific cofactors to induce SHM, suggesting either that it functions alone or that the factors it requires are expressed at other stages of B-cell differentiation. 相似文献
99.
The development of jaws was a critical event in vertebrate evolution because it ushered in a transition to a predatory lifestyle, but how this innovation came about has been a mystery. In the embryos of jawed vertebrates (gnathostomes), the jaw cartilage develops from the mandibular arch, where none of the Hox genes is expressed; if these are expressed ectopically, however, jaw development is inhibited. Here I show that in the lamprey, a primitively jawless (agnathan) fish that is a sister group to the gnathostomes, a Hox gene is expressed in the mandibular arch of developing embryos. This finding, together with outgroup comparisons, suggests that loss of Hox expression from the mandibular arch of gnathostomes may have facilitated the evolution of jaws. 相似文献
100.
Divergence times estimated from molecular data often considerably predate the earliest known fossil representatives of the groups studied. For the order Primates, molecular data calibrated with various external fossil dates uniformly suggest a mid-Cretaceous divergence from other placental mammals, some 90 million years (Myr) ago, whereas the oldest known fossil primates are from the basal Eocene epoch (54-55 Myr ago). The common ancestor of primates should be earlier than the oldest known fossils, but adequate quantification is needed to interpret possible discrepancies between molecular and palaeontological estimates. Here we present a new statistical method, based on an estimate of species preservation derived from a model of the diversification pattern, that suggests a Cretaceous last common ancestor of primates, approximately 81.5 Myr ago, close to the initial divergence time inferred from molecular data. It also suggests that no more than 7% of all primate species that have ever existed are known from fossils. The approach unites all the available palaeontological methods of timing evolutionary events: the fossil record, extant species and clade diversification models. 相似文献