全文获取类型
收费全文 | 296篇 |
免费 | 47篇 |
国内免费 | 1篇 |
出版年
2022年 | 10篇 |
2021年 | 18篇 |
2020年 | 9篇 |
2019年 | 7篇 |
2018年 | 8篇 |
2017年 | 8篇 |
2016年 | 12篇 |
2015年 | 15篇 |
2014年 | 15篇 |
2013年 | 8篇 |
2012年 | 13篇 |
2011年 | 16篇 |
2010年 | 9篇 |
2009年 | 10篇 |
2008年 | 11篇 |
2007年 | 13篇 |
2006年 | 15篇 |
2005年 | 12篇 |
2004年 | 13篇 |
2003年 | 11篇 |
2002年 | 11篇 |
2001年 | 4篇 |
1999年 | 8篇 |
1998年 | 3篇 |
1997年 | 6篇 |
1995年 | 3篇 |
1994年 | 2篇 |
1993年 | 2篇 |
1992年 | 6篇 |
1991年 | 2篇 |
1989年 | 3篇 |
1984年 | 2篇 |
1983年 | 4篇 |
1982年 | 2篇 |
1981年 | 3篇 |
1977年 | 2篇 |
1975年 | 2篇 |
1974年 | 5篇 |
1973年 | 2篇 |
1972年 | 4篇 |
1971年 | 3篇 |
1970年 | 2篇 |
1968年 | 2篇 |
1963年 | 2篇 |
1960年 | 3篇 |
1947年 | 1篇 |
1946年 | 1篇 |
1945年 | 2篇 |
1943年 | 2篇 |
1941年 | 2篇 |
排序方式: 共有344条查询结果,搜索用时 343 毫秒
91.
Xin Huang Alyssa Lyn Fortier Alec J Coffman Travis J Struck Megan N Irby Jennifer E James Jos E Len-Burguete Aaron P Ragsdale Ryan N Gutenkunst 《Molecular biology and evolution》2021,38(10):4588
The effect of a mutation on fitness may differ between populations depending on environmental and genetic context, but little is known about the factors that underlie such differences. To quantify genome-wide correlations in mutation fitness effects, we developed a novel concept called a joint distribution of fitness effects (DFE) between populations. We then proposed a new statistic w to measure the DFE correlation between populations. Using simulation, we showed that inferring the DFE correlation from the joint allele frequency spectrum is statistically precise and robust. Using population genomic data, we inferred DFE correlations of populations in humans, Drosophila melanogaster, and wild tomatoes. In these species, we found that the overall correlation of the joint DFE was inversely related to genetic differentiation. In humans and D. melanogaster, deleterious mutations had a lower DFE correlation than tolerated mutations, indicating a complex joint DFE. Altogether, the DFE correlation can be reliably inferred, and it offers extensive insight into the genetics of population divergence. 相似文献
92.
93.
94.
Julia L. Y. Spaet Rima W. Jabado Aaron C. Henderson Alec B. M. Moore Michael L. Berumen 《Ecology and evolution》2015,5(12):2317-2332
The northwestern Indian Ocean harbors a number of larger marine vertebrate taxa that warrant the investigation of genetic population structure given remarkable spatial heterogeneity in biological characteristics such as distribution, behavior, and morphology. Here, we investigate the genetic population structure of four commercially exploited shark species with different biological characteristics (Carcharhinus limbatus, Carcharhinus sorrah, Rhizoprionodon acutus, and Sphyrna lewini) between the Red Sea and all other water bodies surrounding the Arabian Peninsula. To assess intraspecific patterns of connectivity, we constructed statistical parsimony networks among haplotypes and estimated (1) population structure; and (2) time of most recent population expansion, based on mitochondrial control region DNA and a total of 20 microsatellites. Our analysis indicates that, even in smaller, less vagile shark species, there are no contemporary barriers to gene flow across the study region, while historical events, for example, Pleistocene glacial cycles, may have affected connectivity in C. sorrah and R. acutus. A parsimony network analysis provided evidence that Arabian S. lewini may represent a population segment that is distinct from other known stocks in the Indian Ocean, raising a new layer of conservation concern. Our results call for urgent regional cooperation to ensure the sustainable exploitation of sharks in the Arabian region. 相似文献
95.
Ravi K Amaravadi Eric H Baehrecke Francesco Cecconi Patrice Codogno Jayanta Debnath David A Gewirtz Vassiliki Karantza Alec Kimmelman Sharad Kumar Beth Levine Maria Chiara Maiuri Seamus J Martin Josef Penninger Mauro Piacentini David C Rubinsztein Hans‐Uwe Simon Anne Simonsen Andrew M Thorburn Guillermo Velasco Guido Kroemer 《The EMBO journal》2015,34(7):856-880
Autophagy plays a key role in the maintenance of cellular homeostasis. In healthy cells, such a homeostatic activity constitutes a robust barrier against malignant transformation. Accordingly, many oncoproteins inhibit, and several oncosuppressor proteins promote, autophagy. Moreover, autophagy is required for optimal anticancer immunosurveillance. In neoplastic cells, however, autophagic responses constitute a means to cope with intracellular and environmental stress, thus favoring tumor progression. This implies that at least in some cases, oncogenesis proceeds along with a temporary inhibition of autophagy or a gain of molecular functions that antagonize its oncosuppressive activity. Here, we discuss the differential impact of autophagy on distinct phases of tumorigenesis and the implications of this concept for the use of autophagy modulators in cancer therapy. 相似文献
96.
97.
Shilpi Verma Andrea Loewendorf Qiao Wang Bryan McDonald Alec Redwood Chris A. Benedict 《PLoS pathogens》2014,10(8)
TNF-related apoptosis inducing ligand (TRAIL) death receptors (DR) regulate apoptosis and inflammation, but their role in antiviral defense is poorly understood. Cytomegaloviruses (CMV) encode many immune-modulatory genes that shape host immunity, and they utilize multiple strategies to target the TNF-family cytokines. Here we show that the m166 open reading frame (orf) of mouse CMV (MCMV) is strictly required to inhibit expression of TRAIL-DR in infected cells. An MCMV mutant lacking m166 expression (m166stop) is severely compromised for replication in vivo, most notably in the liver, and depleting natural killer (NK) cells, or infecting TRAIL-DR−/− mice, restored MCMV-m166stop replication completely. These results highlight the critical importance for CMV to have evolved a strategy to inhibit TRAIL-DR signaling to thwart NK-mediated defenses. 相似文献
98.
99.
100.
Sundari Chodavarapu Magdalena M. Felczak Lyle A. Simmons Alec Murillo Jon M. Kaguni 《Nucleic acids research》2013,41(22):10254-10267
DnaA is the initiator of DNA replication in bacteria. A mutant DnaA named DnaAcos is unusual because it is refractory to negative regulation. We developed a genetic method to isolate other mutant DnaAs that circumvent regulation to extend our understanding of mechanisms that control replication initiation. Like DnaAcos, one mutant bearing a tyrosine substitution for histidine 202 (H202Y) withstands the regulation exerted by datA, hda and dnaN (β clamp), and both DnaAcos and H202Y resist inhibition by the Hda-β clamp complex in vitro. Other mutant DnaAs carrying G79D, E244K, V303M or E445K substitutions are either only partially sensitive or refractory to inhibition by the Hda-β clamp complex in vitro but are responsive to hda expression in vivo. All mutant DnaAs remain able to interact directly with Hda. Of interest, both DnaAcos and DnaAE244K bind more avidly to Hda. These mutants, by sequestrating Hda, may limit its availability to regulate other DnaA molecules, which remain active to induce extra rounds of DNA replication. Other evidence suggests that a mutant bearing a V292M substitution hyperinitiates by escaping the effect of an unknown regulatory factor. Together, our results provide new insight into the mechanisms that regulate replication initiation in Escherichia coli. 相似文献