全文获取类型
收费全文 | 992篇 |
免费 | 85篇 |
出版年
2023年 | 4篇 |
2022年 | 16篇 |
2021年 | 45篇 |
2020年 | 13篇 |
2019年 | 32篇 |
2018年 | 22篇 |
2017年 | 21篇 |
2016年 | 47篇 |
2015年 | 60篇 |
2014年 | 86篇 |
2013年 | 77篇 |
2012年 | 101篇 |
2011年 | 94篇 |
2010年 | 58篇 |
2009年 | 61篇 |
2008年 | 60篇 |
2007年 | 52篇 |
2006年 | 42篇 |
2005年 | 36篇 |
2004年 | 31篇 |
2003年 | 21篇 |
2002年 | 22篇 |
2001年 | 10篇 |
2000年 | 2篇 |
1999年 | 8篇 |
1998年 | 3篇 |
1997年 | 4篇 |
1996年 | 2篇 |
1995年 | 2篇 |
1994年 | 3篇 |
1993年 | 1篇 |
1992年 | 3篇 |
1991年 | 3篇 |
1990年 | 2篇 |
1989年 | 1篇 |
1988年 | 1篇 |
1987年 | 2篇 |
1986年 | 5篇 |
1985年 | 1篇 |
1983年 | 1篇 |
1982年 | 2篇 |
1981年 | 4篇 |
1980年 | 1篇 |
1979年 | 3篇 |
1978年 | 3篇 |
1975年 | 3篇 |
1974年 | 3篇 |
1973年 | 3篇 |
排序方式: 共有1077条查询结果,搜索用时 171 毫秒
81.
Adaptation to adverse environmental conditions such as high altitude requires physiological and/or morphological changes. Genome scans provide a means to identify the genetic basis of such adaptations without previous knowledge about the particular genetic variants or traits under selection. In this study, we scanned 3027 amplified fragment length polymorphisms (AFLP) in four populations of the common vole Microtus arvalis for loci associated with local adaptation and high altitude. We investigated voles from two populations at high elevation (~2000 m a.s.l.) representing the upper limit of the altitudinal distribution of the species and two geographically close low-altitude populations (<600 m a.s.l.). Statistical analysis incorporated a new Bayesian F(ST) outlier approach specifically developed for AFLP markers, which considers the intensity of AFLP bands instead of mere presence/absence and allows to derive population-based estimates of allele frequencies and F(IS) values. Computer simulations showed that this approach increases the statistical power of the detection of AFLP markers under selection almost to the power of single nucleotide polymorphism (SNP) data without compromising specificity. Our enhanced genome scan resulted in 20 prime candidate markers for positive selection, which show mostly extremely high allele frequency differences between the low- and high-altitude populations. The comparison of global- and pairwise-enhanced genome scans demonstrated further that very strong selective signatures may also be associated with single populations suggesting the importance of local adaptation in alpine populations of common voles. 相似文献
82.
Martini E Borde V Legendre M Audic S Regnault B Soubigou G Dujon B Llorente B 《PLoS genetics》2011,7(9):e1002305
Meiotic DNA double-strand breaks (DSBs) initiate crossover (CO) recombination, which is necessary for accurate chromosome segregation, but DSBs may also repair as non-crossovers (NCOs). Multiple recombination pathways with specific intermediates are expected to lead to COs and NCOs. We revisited the mechanisms of meiotic DSB repair and the regulation of CO formation, by conducting a genome-wide analysis of strand-transfer intermediates associated with recombination events. We performed this analysis in a SK1 × S288C Saccharomyces cerevisiae hybrid lacking the mismatch repair (MMR) protein Msh2, to allow efficient detection of heteroduplex DNAs (hDNAs). First, we observed that the anti-recombinogenic activity of MMR is responsible for a 20% drop in CO number, suggesting that in MMR-proficient cells some DSBs are repaired using the sister chromatid as a template when polymorphisms are present. Second, we observed that a large fraction of NCOs were associated with trans-hDNA tracts constrained to a single chromatid. This unexpected finding is compatible with dissolution of double Holliday junctions (dHJs) during repair, and it suggests the existence of a novel control point for CO formation at the level of the dHJ intermediate, in addition to the previously described control point before the dHJ formation step. Finally, we observed that COs are associated with complex hDNA patterns, confirming that the canonical double-strand break repair model is not sufficient to explain the formation of most COs. We propose that multiple factors contribute to the complexity of recombination intermediates. These factors include repair of nicks and double-stranded gaps, template switches between non-sister and sister chromatids, and HJ branch migration. Finally, the good correlation between the strand transfer properties observed in the absence of and in the presence of Msh2 suggests that the intermediates detected in the absence of Msh2 reflect normal intermediates. 相似文献
83.
84.
Sainlos M Tigaret C Poujol C Olivier NB Bard L Breillat C Thiolon K Choquet D Imperiali B 《Nature chemical biology》2011,7(2):81-91
The interactions of the AMPA receptor (AMPAR) auxiliary subunit Stargazin with PDZ domain-containing scaffold proteins such as PSD-95 are critical for the synaptic stabilization of AMPARs. To investigate these interactions, we have developed biomimetic competing ligands that are assembled from two Stargazin-derived PSD-95/DLG/ZO-1 (PDZ) domain-binding motifs using 'click' chemistry. Characterization of the ligands in vitro and in a cellular FRET-based model revealed an enhanced affinity for the multiple PDZ domains of PSD-95 compared to monovalent peptides. In cultured neurons, the divalent ligands competed with transmembrane AMPAR regulatory protein (TARP) for the intracellular membrane-associated guanylate kinase resulting in increased lateral diffusion and endocytosis of surface AMPARs, while showing strong inhibition of synaptic AMPAR currents. This provides evidence for a model in which the TARP-containing AMPARs are stabilized at the synapse by engaging in multivalent interactions. In light of the prevalence of PDZ domain clusters, these new biomimetic chemical tools could find broad application for acutely perturbing multivalent complexes. 相似文献
85.
Guillaume Gayet Cyril Eraud Maurice Benmergui Joël Broyer François Mesleard Hervé Fritz Matthieu Guillemain 《European Journal of Wildlife Research》2011,57(5):1051-1056
A number of native and exotic animal species show dramatic population increases in terms of both numbers and geographic range.
Understanding the habitat selection processes behind such increases is crucial to implement adequate management measures.
Mute swan (Cygnus olor) populations have experienced a tremendous demographic and geographic expansion in Western Europe during the twentieth century,
colonizing a wide variety of aquatic habitats. We aimed at assessing how swans select nesting sites during the pre-laying
and laying periods on medium to large fishponds (from 10 to 50 ha) in Eastern France, while accounting for detectability biases
and testing for the effects of fishpond spatial configuration, vegetation resources, human disturbance and habitat management.
Our results demonstrate that the mute swan is a non-selective species regarding its nesting habitat among such fishponds,
using these independently from the parameters considered although fishpond characteristics varied. Although mute swan is one
of the least cryptic Anatidae, owing to its white colour and large size, detection of breeding pairs remained imperfect for
each over several sampling occasions. However, because we repeated the sampling sessions, detection of swan pairs by the end
of the monitoring period was as high as 0.94. These results are consistent with previous assertions that the mute swan is
a species of high ecological plasticity, which may partly explain its recent colonization rates. Given that even swan breeding
events were imperfectly detected on each occasion, we highlight the fact that most studies of breeding ducks (which are more
cryptic) would be considerably improved by better considering detection biases. 相似文献
86.
There is now ample evidence that plant development, responses to abiotic environments, and immune responses are tightly intertwined in their physiology. Thus optimization of the immune system during evolution will occur in coordination with that of plant development. Two alternative and possibly complementary forces are at play: genetic constraints due to the pleiotropic action of players in both systems, and coevolution, if developmental changes modulate the cost-benefit balance of immunity. A current challenge is to elucidate the ecological forces driving evolution of quantitative variation for defense at molecular level. The analysis of natural co-variation for developmental and immunity traits in Arabidopsis thaliana promises to bring important insights. 相似文献
87.
88.
Genome-Wide Association Studies are powerful tools to detect genetic variants associated with diseases. Their results have, however, been questioned, in part because of the bias induced by population stratification. This is a consequence of systematic differences in allele frequencies due to the difference in sample ancestries that can lead to both false positive or false negative findings. Many strategies are available to account for stratification but their performances differ, for instance according to the type of population structure, the disease susceptibility locus minor allele frequency, the degree of sampling imbalanced, or the sample size. We focus on the type of population structure and propose a comparison of the most commonly used methods to deal with stratification that are the Genomic Control, Principal Component based methods such as implemented in Eigenstrat, adjusted Regressions and Meta-Analyses strategies. Our assessment of the methods is based on a large simulation study, involving several scenarios corresponding to many types of population structures. We focused on both false positive rate and power to determine which methods perform the best. Our analysis showed that if there is no population structure, none of the tests led to a bias nor decreased the power except for the Meta-Analyses. When the population is stratified, adjusted Logistic Regressions and Eigenstrat are the best solutions to account for stratification even though only the Logistic Regressions are able to constantly maintain correct false positive rates. This study provides more details about these methods. Their advantages and limitations in different stratification scenarios are highlighted in order to propose practical guidelines to account for population stratification in Genome-Wide Association Studies. 相似文献
89.
90.