全文获取类型
收费全文 | 11360篇 |
免费 | 920篇 |
国内免费 | 8篇 |
出版年
2022年 | 38篇 |
2021年 | 102篇 |
2020年 | 53篇 |
2019年 | 89篇 |
2018年 | 133篇 |
2017年 | 147篇 |
2016年 | 209篇 |
2015年 | 360篇 |
2014年 | 388篇 |
2013年 | 530篇 |
2012年 | 642篇 |
2011年 | 668篇 |
2010年 | 454篇 |
2009年 | 444篇 |
2008年 | 592篇 |
2007年 | 686篇 |
2006年 | 649篇 |
2005年 | 652篇 |
2004年 | 620篇 |
2003年 | 628篇 |
2002年 | 637篇 |
2001年 | 161篇 |
2000年 | 146篇 |
1999年 | 188篇 |
1998年 | 218篇 |
1997年 | 170篇 |
1996年 | 145篇 |
1995年 | 145篇 |
1994年 | 134篇 |
1993年 | 156篇 |
1992年 | 189篇 |
1991年 | 144篇 |
1990年 | 153篇 |
1989年 | 121篇 |
1988年 | 107篇 |
1987年 | 98篇 |
1986年 | 80篇 |
1985年 | 116篇 |
1984年 | 107篇 |
1983年 | 84篇 |
1982年 | 98篇 |
1981年 | 85篇 |
1980年 | 81篇 |
1979年 | 79篇 |
1978年 | 61篇 |
1977年 | 77篇 |
1976年 | 73篇 |
1975年 | 45篇 |
1974年 | 51篇 |
1973年 | 50篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
991.
992.
Robert J. Gleave Daryl S. Walter Paul J. Beswick Elena Fonfria Anton D. Michel Shilina A. Roman Sac-Pham Tang 《Bioorganic & medicinal chemistry letters》2010,20(16):4951-4954
A series of analogues of the pyrazole lead 1 were synthesized in which the heterocyclic core was replaced with an imidazole. A number of potent antagonists were identified and structure–activity relationships (SAR) were investigated both with respect to activity at the P2X7 receptor and in vitro metabolic stability. Compound 10 was identified as a potent P2X7 antagonist with reduced in vitro metabolism and high solubility. 相似文献
993.
994.
995.
Alexandre Hinzpeter Abdel Aissat Elvira Sondo Catherine Costa Nicole Arous Christine Gameiro Natacha Martin Agathe Tarze Laurence Weiss Alix de Becdelièvre Bruno Costes Michel Goossens Luis J. Galietta Emmanuelle Girodon Pascale Fanen 《PLoS genetics》2010,6(10)
Approximately 30% of alleles causing genetic disorders generate premature termination codons (PTCs), which are usually associated with severe phenotypes. However, bypassing the deleterious stop codon can lead to a mild disease outcome. Splicing at NAGNAG tandem splice sites has been reported to result in insertion or deletion (indel) of three nucleotides. We identified such a mechanism as the origin of the mild to asymptomatic phenotype observed in cystic fibrosis patients homozygous for the E831X mutation (2623G>T) in the CFTR gene. Analyses performed on nasal epithelial cell mRNA detected three distinct isoforms, a considerably more complex situation than expected for a single nucleotide substitution. Structure-function studies and in silico analyses provided the first experimental evidence of an indel of a stop codon by alternative splicing at a NAGNAG acceptor site. In addition to contributing to proteome plasticity, alternative splicing at a NAGNAG tandem site can thus remove a disease-causing UAG stop codon. This molecular study reveals a naturally occurring mechanism where the effect of either modifier genes or epigenetic factors could be suspected. This finding is of importance for genetic counseling as well as for deciding appropriate therapeutic strategies. 相似文献
996.
Gaudet MM Kirchhoff T Green T Vijai J Korn JM Guiducci C Segrè AV McGee K McGuffog L Kartsonaki C Morrison J Healey S Sinilnikova OM Stoppa-Lyonnet D Mazoyer S Gauthier-Villars M Sobol H Longy M Frenay M GEMO Study Collaborators Hogervorst FB Rookus MA Collée JM Hoogerbrugge N van Roozendaal KE;HEBON Study Collaborators Piedmonte M Rubinstein W Nerenstone S Van Le L Blank SV Caldés T de la Hoya M Nevanlinna H Aittomäki K Lazaro C Blanco I Arason A Johannsson OT Barkardottir RB Devilee P 《PLoS genetics》2010,6(10):e1001183
The considerable uncertainty regarding cancer risks associated with inherited mutations of BRCA2 is due to unknown factors. To investigate whether common genetic variants modify penetrance for BRCA2 mutation carriers, we undertook a two-staged genome-wide association study in BRCA2 mutation carriers. In stage 1 using the Affymetrix 6.0 platform, 592,163 filtered SNPs genotyped were available on 899 young (<40 years) affected and 804 unaffected carriers of European ancestry. Associations were evaluated using a survival-based score test adjusted for familial correlations and stratified by country of the study and BRCA2*6174delT mutation status. The genomic inflation factor (λ) was 1.011. The stage 1 association analysis revealed multiple variants associated with breast cancer risk: 3 SNPs had p-values<10(-5) and 39 SNPs had p-values<10(-4). These variants included several previously associated with sporadic breast cancer risk and two novel loci on chromosome 20 (rs311499) and chromosome 10 (rs16917302). The chromosome 10 locus was in ZNF365, which contains another variant that has recently been associated with breast cancer in an independent study of unselected cases. In stage 2, the top 85 loci from stage 1 were genotyped in 1,264 cases and 1,222 controls. Hazard ratios (HR) and 95% confidence intervals (CI) for stage 1 and 2 were combined and estimated using a retrospective likelihood approach, stratified by country of residence and the most common mutation, BRCA2*6174delT. The combined per allele HR of the minor allele for the novel loci rs16917302 was 0.75 (95% CI 0.66-0.86, ) and for rs311499 was 0.72 (95% CI 0.61-0.85, ). FGFR2 rs2981575 had the strongest association with breast cancer risk (per allele HR = 1.28, 95% CI 1.18-1.39, ). These results indicate that SNPs that modify BRCA2 penetrance identified by an agnostic approach thus far are limited to variants that also modify risk of sporadic BRCA2 wild-type breast cancer. 相似文献
997.
The pathogenic chytrid fungus Batrachochytrium dendrobatidis (Bd) is considered responsible for the population declines and extinctions of hundreds of amphibian species worldwide. The panzootic
was likely triggered by human-assisted spread, but once the pathogen becomes established in a given region, its distribution
is probably determined by local drivers. To assess the relative importance of potential drivers of infection in red-spotted
newts (Notophthalmus viridescens), we measured Bd levels in 16 populations throughout central Pennsylvania. Infected individuals were detected in all but four populations,
indicating that Bd is widespread in this region. We quantified local factors hypothesized to influence Bd, and found that infection levels were best predicted by the proportion of the pond substrate consisting of leaf litter or
vegetation, along with a significant effect of water temperature. Bd infection in amphibians is temperature-dependent, and one possible explanation of the apparent substrate effect is that tree
cover and vegetation provide shade, reducing the availability of shallow, warm-water patches in which newts might reduce or
clear Bd infections. Alternatively, leaf litter and emergent vegetation might increase Bd infection more directly, perhaps by providing substrates for environmental growth of the fungus. We also observed a curvilinear
relationship between Bd load and snout-vent length (a proxy for age), hinting that newts might develop acquired resistance to Bd infection. Though correlational, these results add to a growing body of evidence suggesting that environmental temperature
is an important driver of Bd infection dynamics. 相似文献
998.
999.
Thibaud Souter Raphael Cornette Julio Pedraza John Hutchinson Michel Baylac 《Comptes Rendus Palevol》2010,9(6-7):411-422
Geometric morphometrics involves defining landmark points to generate a discrete representation of an object. This crucial step is strongly influenced by the biological question guiding the analysis, and even more when using curve and surface semi-landmarks methods, because these require to generate a template of reference. We exemplify these constraints using two datasets from projects with very different backgrounds. The Theropod Dataset is a functional morphometric analysis of different extinct and extant theropod pelves. The Shrew Dataset is a populational morphometric analysis of the white-toothed shrew with very small variations in skull shape. We propose a novel procedure to generate a regular template configuration, using polygonal modelling tools. This method allows us to control the template geometry and adapt its complexity to the morphological variation in the sample. More studies are necessary to assess the morphometric and statistical importance of template design in curve and surface analyses. 相似文献
1000.
Michel Veuille 《Comptes rendus biologies》2010,333(2):145-156
Darwin's book on the Descent of Man and Selection in Relation to Sex (1871) is often viewed as the continuation of TheOrigin of Species published 12 years earlier (1859), both because of the implicit parallelism between natural selection and sexual selection, and because Darwin himself presents the book as developing a subject (man) which he intentionally omitted in the Origin. But the Descent can also be viewed as the continuation of his book on Variation published three years earlier (1868). Firstly because Darwin's hypothesis of pangenesis links the selection process to the origin of variation through use and disuse, an idea underlying his speculations on the origin of moral sense in humans. Second because like the action of the horticulturist on his domestic crops, sexual selection exerted by one sex on the other sex can develop fancy traits that are not easily accounted for by their utility to the selected organism itself, such as artistic taste, pride, courage, and the morphological differences between human populations. These traits are difficult to reconcile with pangenesis. They add up to other contradictions of the book possibly resulting from Darwin's erroneous inference about the mechanism of inheritance, like those on the determination of sex-ratio, or the confusion between individual adaptation and the advantage to the species. These inconsistencies inaugurate a weakening of the Darwinian message, which will last 50 years after his death. They contributed to the neglect of sexual selection for a century. Darwin however maintained a logical distinction between evolutionary mechanisms and hereditary mechanisms, and an epistemological distinction between evolutionary theory and Pangenesis hypothesis. In the modern context of Mendelian genetics, Darwin's sexual selection retrospectively appears as luminous an idea in its pure principle as natural selection, even though the mechanisms governing the evolution of sexual choice in animals remain largely unresolved. 相似文献