全文获取类型
收费全文 | 326篇 |
免费 | 42篇 |
国内免费 | 1篇 |
出版年
2022年 | 2篇 |
2021年 | 5篇 |
2019年 | 3篇 |
2018年 | 5篇 |
2017年 | 3篇 |
2016年 | 7篇 |
2015年 | 16篇 |
2014年 | 13篇 |
2013年 | 13篇 |
2012年 | 6篇 |
2011年 | 14篇 |
2010年 | 10篇 |
2009年 | 17篇 |
2008年 | 9篇 |
2007年 | 11篇 |
2006年 | 10篇 |
2005年 | 15篇 |
2004年 | 19篇 |
2003年 | 12篇 |
2002年 | 6篇 |
2001年 | 7篇 |
2000年 | 11篇 |
1999年 | 12篇 |
1998年 | 12篇 |
1997年 | 7篇 |
1996年 | 4篇 |
1995年 | 5篇 |
1994年 | 6篇 |
1993年 | 6篇 |
1992年 | 8篇 |
1991年 | 2篇 |
1990年 | 10篇 |
1989年 | 12篇 |
1988年 | 7篇 |
1987年 | 6篇 |
1986年 | 11篇 |
1985年 | 7篇 |
1984年 | 3篇 |
1983年 | 2篇 |
1982年 | 2篇 |
1977年 | 4篇 |
1975年 | 2篇 |
1973年 | 3篇 |
1970年 | 2篇 |
1969年 | 4篇 |
1967年 | 2篇 |
1966年 | 3篇 |
1954年 | 1篇 |
1936年 | 1篇 |
1912年 | 1篇 |
排序方式: 共有369条查询结果,搜索用时 15 毫秒
31.
Gould CJ Maiti S Michelot A Graziano BR Blanchoin L Goode BL 《Current biology : CB》2011,21(5):384-390
Formins are a large family of actin assembly-promoting proteins with many important biological roles. However, it has remained unclear how formins nucleate actin polymerization. All other nucleators are known to recruit actin monomers as a central part of their mechanisms. However, the actin-nucleating FH2 domain of formins lacks appreciable affinity for monomeric actin. Here, we found that yeast and mammalian formins bind actin monomers but that this activity requires their C-terminal DAD domains. Furthermore, we observed that the DAD works in concert with the FH2 to enhance nucleation without affecting the rate of filament elongation. We dissected this mechanism in mDia1, mapped nucleation activity to conserved residues in the DAD, and demonstrated that DAD roles in nucleation and autoinhibition are separable. Furthermore, DAD enhancement of nucleation was independent of contributions from the FH1 domain to nucleation. Together, our data show that (1) the DAD has dual functions in autoinhibition and nucleation; (2) the FH1, FH2, and DAD form a tripartite nucleation machine; and (3) formins nucleate by recruiting actin monomers and therefore are more similar to other nucleators than previously thought. 相似文献
32.
Background
PCR-based surveys have shown that guppies (Poecilia reticulata) have an unusually large visual-opsin gene repertoire. This has led to speculation that opsin duplication and divergence has enhanced the evolution of elaborate male coloration because it improves spectral sensitivity and/or discrimination in females. However, this conjecture on evolutionary connections between opsin repertoire, vision, mate choice, and male coloration was generated with little data on gene expression. Here, we used RT-qPCR to survey visual-opsin gene expression in the eyes of males, females, and juveniles in order to further understand color-based sexual selection from the perspective of the visual system. 相似文献33.
Brown NF Coombes BK Bishop JL Wickham ME Lowden MJ Gal-Mor O Goode DL Boyle EC Sanderson KL Finlay BB 《PloS one》2011,6(3):e17824
Salmonella enterica is a species of bacteria that is a major cause of enteritis across the globe, while certain serovars cause typhoid, a more serious disease associated with a significant mortality rate. Type III secreted effectors are major contributors to the pathogenesis of Salmonella infections. Genes encoding effectors are acquired via horizontal gene transfer, and a subset are encoded within active phage lysogens. Because the acquisition of effectors is in flux, the complement of effectors possessed by various Salmonella strains frequently differs. By comparing the genome sequences of S. enterica serovar Typhimurium strain SL1344 with LT2, we identified a gene with significant similarity to SseK/NleB type III secreted effector proteins within a phage ST64B lysogen that is absent from LT2. We have named this gene sseK3. SseK3 was co-regulated with the SPI-2 type III secretion system in vitro and inside host cells, and was also injected into infected host cells. While no role for SseK3 in virulence could be identified, a role for the other family members in murine typhoid was found. SseK3 and other phage-encoded effectors were found to have a significant but sparse distribution in the available Salmonella genome sequences, indicating the potential for more uncharacterised effectors to be present in less studied serovars. These phage-encoded effectors may be principle subjects of contemporary selective processes shaping Salmonella-host interactions. 相似文献
34.
35.
36.
Many investigators of complexly inherited familial traits bypass classical segregation analysis to perform model-free genome-wide linkage scans. Because model-based or parametric linkage analysis may be the most powerful means to localize genes when a model can be approximated, model-free statistics may result in a loss of power to detect linkage. We performed limited segregation analyses on the electrophysiological measurements that have been collected for the Collaborative Study on the Genetics of Alcoholism. The resulting models are used in whole-genome scans. Four genomic regions provided a model-based LOD > 2 and only 3 of these were detected (p < 0.05) by a model-free approach. We conclude that parametric methods, using even over-simplified models of complex phenotypes, may complement nonparametric methods and decrease false positives. 相似文献
37.
38.
Dissection of Arp2/3 complex actin nucleation mechanism and distinct roles for its nucleation-promoting factors in Saccharomyces cerevisiae 总被引:3,自引:0,他引:3 下载免费PDF全文
Actin nucleation by the Arp2/3 complex is under tight control, remaining inactive until stimulation by nucleation-promoting factors (NPFs). Although multiple NPFs are expressed in most cell types, little is known about how they are coordinated and whether they perform similar or distinct functions. We examined genetic relationships among the four S. cerevisiae NPFs. Combining las17delta with pan1-101 or myo3delta myo5delta was lethal at all temperatures, whereas combining pan1-101 with myo3delta myo5delta showed no genetic interaction and abp1delta partially suppressed las17delta. These data suggest that NPFs have distinct and overlapping functions in vivo. We also tested genetic interactions between each NPF mutant and seven different temperature-sensitive arp2 alleles and purified mutant Arp2/3 complexes to compare their activities. Two arp2 alleles with mutations at the barbed end were severely impaired in nucleation, providing the first experimental evidence that Arp2 nucleates actin at its barbed end in vitro and in vivo. Another arp2 allele caused partially unregulated ("leaky") nucleation in the absence of NPFs. Combining this mutant with a partially unregulated allele in a different subunit of Arp2/3 complex was lethal, suggesting that cells cannot tolerate high levels of unregulated activity. Genetic interactions between arp2 alleles and NPF mutants point to Abp1 having an antagonistic role with respect to other NPFs, possibly serving to attenuate their stronger activities. In support of this model, Abp1 binds strongly to Arp2/3 complex, yet has notably weak nucleation-promoting activity and inhibits Las17 activity on Arp2/3 complex in a dose-responsive manner. 相似文献
39.
Furge LL Fields PR Goode WE Konwinski RR Tressler MC Stevens-Truss R 《Archives of biochemistry and biophysics》2004,424(2):163-170
The clinically relevant drug oltipraz (OPZ) has previously been shown to inhibit cytochrome P450 enzymes [Chem. Res. Toxicol. 13 (2000) 245]. The current study reveals that OPZ is also able to inhibit *NO formation by purified inducible nitric oxide synthase (iNOS) but not by neuronal nitric oxide synthase in hemoglobin assays. The inhibition of iNOS by OPZ is reversible and competitive with an IC(50) of 5.9 microM and Ki of 0.6 microM. In murine BV-2 microglial cells, an immortalized cell line that produces *NO in response to lipopolysaccharide (LPS), OPZ is able to block the formation of nitrite in LPS treated cells. The inhibitory effect of OPZ on LPS treated cells is not due to cell toxicity. Finally, treatment of cells with OPZ does not induce or suppress expression of iNOS protein as shown by Western blot analysis. 相似文献
40.
Yvonne J.K. Edwards Klaudia Walter Gayle McEwen Tanya Vavouri Krystyna A. Kelly Irina Abnizova Adam Woolfe Debbie K. Goode Martin Goodson Phil North Phil Snell Heather Callaway Sarah F. Smith Walter R. Gilks Julie E. Cooke Greg Elgar 《Comparative biochemistry and physiology. Part D, Genomics & proteomics》2006,1(1):46