全文获取类型
收费全文 | 1518篇 |
免费 | 109篇 |
国内免费 | 1篇 |
出版年
2023年 | 15篇 |
2022年 | 19篇 |
2021年 | 44篇 |
2020年 | 29篇 |
2019年 | 37篇 |
2018年 | 54篇 |
2017年 | 43篇 |
2016年 | 45篇 |
2015年 | 104篇 |
2014年 | 72篇 |
2013年 | 111篇 |
2012年 | 144篇 |
2011年 | 126篇 |
2010年 | 81篇 |
2009年 | 64篇 |
2008年 | 73篇 |
2007年 | 75篇 |
2006年 | 59篇 |
2005年 | 46篇 |
2004年 | 48篇 |
2003年 | 34篇 |
2002年 | 36篇 |
2001年 | 18篇 |
2000年 | 15篇 |
1999年 | 12篇 |
1998年 | 11篇 |
1997年 | 7篇 |
1995年 | 6篇 |
1992年 | 10篇 |
1991年 | 7篇 |
1990年 | 9篇 |
1989年 | 12篇 |
1988年 | 12篇 |
1987年 | 13篇 |
1986年 | 6篇 |
1985年 | 9篇 |
1984年 | 6篇 |
1983年 | 8篇 |
1979年 | 5篇 |
1978年 | 5篇 |
1977年 | 6篇 |
1975年 | 10篇 |
1974年 | 9篇 |
1973年 | 8篇 |
1972年 | 6篇 |
1971年 | 5篇 |
1969年 | 5篇 |
1968年 | 9篇 |
1967年 | 7篇 |
1966年 | 8篇 |
排序方式: 共有1628条查询结果,搜索用时 15 毫秒
121.
122.
Demographic inferences using short‐read genomic data in an approximate Bayesian computation framework: in silico evaluation of power,biases and proof of concept in Atlantic walrus
下载免费PDF全文
![点击此处可从《Molecular ecology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Aaron B. A. Shafer Lucie M. Gattepaille Robert E. A. Stewart Jochen B. W. Wolf 《Molecular ecology》2015,24(2):328-345
Approximate Bayesian computation (ABC) is a powerful tool for model‐based inference of demographic histories from large genetic data sets. For most organisms, its implementation has been hampered by the lack of sufficient genetic data. Genotyping‐by‐sequencing (GBS) provides cheap genome‐scale data to fill this gap, but its potential has not fully been exploited. Here, we explored power, precision and biases of a coalescent‐based ABC approach where GBS data were modelled with either a population mutation parameter (θ) or a fixed site (FS) approach, allowing single or several segregating sites per locus. With simulated data ranging from 500 to 50 000 loci, a variety of demographic models could be reliably inferred across a range of timescales and migration scenarios. Posterior estimates were informative with 1000 loci for migration and split time in simple population divergence models. In more complex models, posterior distributions were wide and almost reverted to the uninformative prior even with 50 000 loci. ABC parameter estimates, however, were generally more accurate than an alternative composite‐likelihood method. Bottleneck scenarios proved particularly difficult, and only recent bottlenecks without recovery could be reliably detected and dated. Notably, minor‐allele‐frequency filters – usual practice for GBS data – negatively affected nearly all estimates. With this in mind, we used a combination of FS and θ approaches on empirical GBS data generated from the Atlantic walrus (Odobenus rosmarus rosmarus), collectively providing support for a population split before the last glacial maximum followed by asymmetrical migration and a high Arctic bottleneck. Overall, this study evaluates the potential and limitations of GBS data in an ABC‐coalescence framework and proposes a best‐practice approach. 相似文献
123.
Roberto Mendoza-Londono Somayyeh Fahiminiya Jacek Majewski CareRare Canada Consortium Martine Tétreault Javad Nadaf Peter Kannu Etienne Sochett Andrew Howard Jennifer Stimec Lucie Dupuis Paul Roschger Klaus Klaushofer Telma Palomo Jean Ouellet Hadil Al-Jallad John?S. Mort Pierre Moffatt Sergei Boudko Hans-Peter B?chinger Frank Rauch 《American journal of human genetics》2015,96(6):979-985
Secreted protein, acidic, cysteine-rich (SPARC) is a glycoprotein that binds to collagen type I and other proteins in the extracellular matrix. Using whole-exome sequencing to identify the molecular defect in two unrelated girls with severe bone fragility and a clinical diagnosis of osteogenesis imperfecta type IV, we identified two homozygous variants in SPARC (GenBank: ; c.497G>A [p.Arg166His] in individual 1; c.787G>A [p.Glu263Lys] in individual 2). Published modeling and site-directed mutagenesis studies had previously shown that the residues substituted by these mutations form an intramolecular salt bridge in SPARC and are essential for the binding of SPARC to collagen type I. The amount of SPARC secreted by skin fibroblasts was reduced in individual 1 but appeared normal in individual 2. The migration of collagen type I alpha chains produced by these fibroblasts was mildly delayed on SDS-PAGE gel, suggesting some overmodification of collagen during triple helical formation. Pulse-chase experiments showed that collagen type I secretion was mildly delayed in skin fibroblasts from both individuals. Analysis of an iliac bone sample from individual 2 showed that trabecular bone was hypermineralized on the material level. In conclusion, these observations show that homozygous mutations in SPARC can give rise to severe bone fragility in humans. NM_003118.3相似文献
124.
Beno?te Bourdin Behzad Shakeri Marie-Philippe Tétreault Rémy Sauvé Sylvie Lesage Lucie Parent 《The Journal of biological chemistry》2015,290(5):2854-2869
L-type Ca2+ channels play a critical role in cardiac rhythmicity. These ion channels are oligomeric complexes formed by the pore-forming CaVα1 with the auxiliary CaVβ and CaVα2δ subunits. CaVα2δ increases the peak current density and improves the voltage-dependent activation gating of CaV1.2 channels without increasing the surface expression of the CaVα1 subunit. The functional impact of genetic variants of CACNA2D1 (the gene encoding for CaVα2δ), associated with shorter repolarization QT intervals (the time interval between the Q and the T waves on the cardiac electrocardiogram), was investigated after recombinant expression of the full complement of L-type CaV1.2 subunits in human embryonic kidney 293 cells. By performing side-by-side high resolution flow cytometry assays and whole-cell patch clamp recordings, we revealed that the surface density of the CaVα2δ wild-type protein correlates with the peak current density. Furthermore, the cell surface density of CaVα2δ mutants S755T, Q917H, and S956T was not significantly different from the cell surface density of the CaVα2δ wild-type protein expressed under the same conditions. In contrast, the cell surface expression of CaVα2δ D550Y, CaVα2δ S709N, and the double mutant D550Y/Q917H was reduced, respectively, by ≈30–33% for the single mutants and by 60% for the latter. The cell surface density of D550Y/Q917H was more significantly impaired than protein stability, suggesting that surface trafficking of CaVα2δ was disrupted by the double mutation. Co-expression with D550Y/Q917H significantly decreased CaV1.2 currents as compared with results obtained with CaVα2δ wild type. It is concluded that D550Y/Q917H reduced inward Ca2+ currents through a defect in the cell surface trafficking of CaVα2δ. Altogether, our results provide novel insight in the molecular mechanism underlying the modulation of CaV1.2 currents by CaVα2δ. 相似文献
125.
126.
127.
Ippei Kanazawa Lucie Canaff Jad Abi Rafeh Aarti Angrula Jingjing Li Ryan C. Riddle Iris Boraschi-Diaz Svetlana V. Komarova Thomas L. Clemens Monzur Murshed Geoffrey N. Hendy 《The Journal of biological chemistry》2015,290(7):3910-3924
Menin, the product of the multiple endocrine neoplasia type 1 (Men1) tumor suppressor gene, mediates the cell proliferation and differentiation actions of transforming growth factor-β (TGF-β) ligand family members. In vitro, menin modulates osteoblastogenesis and osteoblast differentiation promoted and sustained by bone morphogenetic protein-2 (BMP-2) and TGF-β, respectively. To examine the in vivo function of menin in bone, we conditionally inactivated Men1 in mature osteoblasts by crossing osteocalcin (OC)-Cre mice with floxed Men1 (Men1f/f) mice to generate mice lacking menin in differentiating osteoblasts (OC-Cre;Men1f/f mice). These mice displayed significant reduction in bone mineral density, trabecular bone volume, and cortical bone thickness compared with control littermates. Osteoblast and osteoclast number as well as mineral apposition rate were significantly reduced, whereas osteocyte number was increased. Primary calvarial osteoblasts proliferated more quickly but had deficient mineral apposition and alkaline phosphatase activity. Although the mRNA expression of osteoblast marker and cyclin-dependent kinase inhibitor genes were all reduced, that of cyclin-dependent kinase, osteocyte marker, and pro-apoptotic genes were increased in isolated Men1 knock-out osteoblasts compared with controls. In contrast to the knock-out mice, transgenic mice overexpressing a human menin cDNA in osteoblasts driven by the 2.3-kb Col1a1 promoter, showed a gain of bone mass relative to control littermates. Osteoblast number and mineral apposition rate were significantly increased in the Col1a1-Menin-Tg mice. Therefore, osteoblast menin plays a key role in bone development, remodeling, and maintenance. 相似文献
128.
129.
The effects of plant traits on species' responses to present and historical patch configurations and patch age
下载免费PDF全文
![点击此处可从《Oikos》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Patch configuration is viewed as an important factor affecting the distributions of plant species. Although a number of studies have explored the relationship between plant life‐history traits and species’ distributions in fragmented landscapes, the effect of individual traits on the dependence of species on historical versus current landscape configurations remains unclear. We identified the extent to which present (2000s) and historical (1843, 1954, 1980s) patch configurations (area and connectivity) and patch age affected the distributions of 99 species inhabiting dry calcareous grasslands. We used traits related to dispersal, survival, growth and habitat preferences to explain the dependence of 60 of these species on present and historical configurations, and the age of grassland patches. We found that most of the species had an affinity to currently or historically large, older and more isolated patches. This suggests that many dry grassland species are not in equilibrium with the current landscape, as their distributions still reflect past landscape structures. Rapidly growing species with higher seed bank longevity and nutrient requirements primarily occur in young, large grassland patches whereas species with the opposite traits occur in older, historically large and currently more isolated smaller patches. We hypothesise that patch quality is the reason why different species occupy patches of different age. Species occupying young, large patches commonly disperse by endozoochory. By contrast, no dispersal trait is associated with species occupying old, usually isolated patches. Our results suggest that species occupying old patches are exposed to higher potential risk of extinction, as their distributions are probably limited by the low number and connectivity of available suitable patches and poor dispersal ability. We thus suggest that the dynamics of these species can effectively be supported by improving the quality of young grassland patches. 相似文献
130.
Radka B?ízová Lucie Vaní?ková Mária Fa?arová Sunday Ekesi Michal Hoskovec Blanka Kalinová 《ZooKeys》2015,(540):385-404
Ceratitis
fasciventris, Ceratitis
anonae and Ceratitis
rosa are polyphagous agricultural pests originating from the African continent. The taxonomy of this group (the so-called Ceratitis FAR complex) is unclear. To clarify the taxonomic relationships, male and female-produced volatiles presumably involved in pre-mating communication were studied using comprehensive two-dimensional gas chromatography with time-of-flight mass spectrometry (GC×GC-TOFMS) followed by multivariate analysis, and gas chromatography combined with electroantennographic detection (GC-EAD). GC×GC-TOFMS analyses revealed sex specific differences in produced volatiles. Male volatiles are complex mixtures that differ both qualitatively and quantitatively but share some common compounds. GC-EAD analyses of male volatiles revealed that the antennal sensitivities of females significantly differ in the studied species. No female volatiles elicited antennal responses in males. The results show clear species-specific differences in volatile production and provide complementary information for the distinct delimitation of the putative species by chemotaxonomic markers. 相似文献