全文获取类型
收费全文 | 440篇 |
免费 | 41篇 |
出版年
2023年 | 1篇 |
2021年 | 4篇 |
2020年 | 2篇 |
2019年 | 4篇 |
2018年 | 7篇 |
2017年 | 9篇 |
2016年 | 8篇 |
2015年 | 13篇 |
2014年 | 19篇 |
2013年 | 26篇 |
2012年 | 29篇 |
2011年 | 30篇 |
2010年 | 23篇 |
2009年 | 18篇 |
2008年 | 37篇 |
2007年 | 27篇 |
2006年 | 21篇 |
2005年 | 26篇 |
2004年 | 21篇 |
2003年 | 30篇 |
2002年 | 21篇 |
2001年 | 8篇 |
2000年 | 5篇 |
1999年 | 16篇 |
1998年 | 7篇 |
1997年 | 5篇 |
1996年 | 8篇 |
1995年 | 1篇 |
1994年 | 4篇 |
1993年 | 5篇 |
1992年 | 4篇 |
1991年 | 4篇 |
1990年 | 4篇 |
1989年 | 3篇 |
1988年 | 1篇 |
1987年 | 3篇 |
1984年 | 3篇 |
1983年 | 2篇 |
1982年 | 1篇 |
1981年 | 2篇 |
1980年 | 3篇 |
1979年 | 3篇 |
1978年 | 4篇 |
1975年 | 1篇 |
1974年 | 2篇 |
1973年 | 3篇 |
1972年 | 1篇 |
1971年 | 1篇 |
1964年 | 1篇 |
排序方式: 共有481条查询结果,搜索用时 62 毫秒
51.
Nonhomologous end-joining (NHEJ) is an important pathway for the repair of DNA double-strand breaks (DSBs) and plays a critical role in maintaining genomic stability in mammalian cells. While Ku70/80 (Ku) functions in NHEJ as part of the DNA-dependent protein kinase (DNA-PK), genetic evidence indicates that the role of Ku in NHEJ goes beyond its participation in DNA-PK. Inositol hexakisphosphate (IP6) was previously found to stimulate NHEJ in vitro and Ku was identified as an IP6-binding factor. Through mutational analysis, we identified a bipartite IP6-binding site in Ku and generated IP6-binding mutants that ranged from 1.22% to 58.48% of wild-type binding. Significantly, these Ku IP6-binding mutants were impaired for participation in NHEJ in vitro and we observed a positive correlation between IP6 binding and NHEJ. Ku IP6-binding mutants were separation-of-function mutants that bound DNA and activated DNA-PK as well as wild-type Ku. Our observations identify a hitherto undefined IP6-binding site in Ku and show that this interaction is important for DSB repair by NHEJ in vitro. Moreover, these data indicate that in addition to binding of exposed DNA termini and activation of DNA-PK, the Ku heterodimer plays a role in mammalian NHEJ that is regulated by binding of IP6. 相似文献
52.
53.
Rogers MS Hurtado-Guerrero R Firbank SJ Halcrow MA Dooley DM Phillips SE Knowles PF McPherson MJ 《Biochemistry》2008,47(39):10428-10439
Galactose oxidase (GO) belongs to a class of proteins that self-catalyze assembly of their redox-active cofactors from active site amino acids. Generation of enzymatically active GO appears to require at least four sequential post-translational modifications: cleavage of a secretion signal sequence, copper-dependent cleavage of an N-terminal pro sequence, copper-dependent formation of a C228-Y272 thioether bond, and generation of the Y272 radical. The last two processes were investigated using a truncated protein (termed premat-GO) lacking the pro sequence and purified under copper-free conditions. Reactions of premat-GO with Cu(II) were investigated using optical, EPR, and resonance Raman spectroscopy, SDS-PAGE, and X-ray crystallography. Premat-GO reacted anaerobically with excess Cu(II) to efficiently form the thioether bond but not the Y272 radical. A potential C228-copper coordinated intermediate (lambda max = 406 nm) in the processing reaction, which had not yet formed the C228-Y272 cross-link, was identified from the absorption spectrum. A copper-thiolate protein complex, with copper coordinated to C228, H496, and H581, was also observed in a 3 min anaerobic soak by X-ray crystallography, whereas a 24 h soak revealed the C228-Y272 thioether bond. In solution, addition of oxygenated buffer to premat-GO preincubated with excess Cu(II) generated the Y272 radical state. On the basis of these data, a mechanism for the formation of the C228-Y272 bond and tyrosyl radical generation is proposed. The 406 nm complex is demonstrated to be a catalytically competent processing intermediate under anaerobic conditions. We propose a potential mechanism which is in common with aerobic processing by Cu(II) until the step at which the second electron acceptor is required. 相似文献
54.
Mwanja Wilson W. Armoudlian Audrey S. Wandera Silvester B. Kaufman Les Wu Lizhao Booton Gregory C. Fuerst Paul A. 《Hydrobiologia》2001,458(1-3):55-62
The Lake Victoria Region (LVR) encompasses the large lakes Victoria, Kyoga, Edward, George and Kivu, as well as scores of small satellite lakes within the parent catchments. Taken as a whole, the LVR originally harbored a unique fish fauna that included in excess of 600 endemic species of cichlid fishes. As a result of human influence, including a commercial fishery and the introduction of several exotic species, nearly 200 cichlid species and several endemic genera have become extinct from lakes Victoria and Kyoga. Recently, we have discovered that some of the apparently extinct taxa survive as extant representatives in the satellite lakes. Here, we summarize the findings of our ecological survey of the fish species of the satellite lakes. We also discuss the results of some preliminary genetic analyses, and highlight major genetic and ecological changes in the fish fauna that have taken place in the regional fishery. Minor lakes now play a crucial role in conserving the endangered species of the entire region, and also as living museums of East African ecological history. Our findings allude to the historical importance of minor satellite lakes as natural refugia for the fishes of the Lake Victoria Region, a region characterized by a history of geological and climatic instability. 相似文献
55.
An introduction to the Farm-Scale Evaluations of genetically modified herbicide-tolerant crops 总被引:5,自引:1,他引:4
56.
Morphological changes that take place in peat cultures of several species of rhizobia were examined. These changes seemed to be associated with enhanced survival of cells in peat and after inoculation onto plastic beads, which were used as a model system for seeds. Cell wall changes, in which the periplasmic space appeared to be occluded with electron-dense material, were observed in Rhizobium sp. strain SU343 and Bradyrhizobium lupini WU425 cells after 7 and 14 days in peat, respectively. Nutrient limitation and low O2 concentration in peat are suggested to be factors involved in the induction of the morphological changes. Polyhydroxybutyrate reserves, which were present in broth-cultured cells of both species of rhizobia, were mobilized after transfer into peat but did not appear to influence survival after inoculation onto beads. Enhanced expression of an iron-manganese superoxide dismutase was also observed after the cells were transferred into peat. We conclude that cell wall thickening in rhizobia after transfer from broth cultures into peat is an adaptive response for long-term survival under nutrient-limited conditions in peat. Cells with thickened walls may also be more resistant to other types of stress, such as that encountered on a seed surface. 相似文献
57.
Joanne E Thwaite Les W J Baillie Noel M Carter Keith Stephenson Mark Rees Colin R Harwood Peter T Emmerson 《Applied and environmental microbiology》2002,68(1):227-234
The stability of heterologous proteins secreted by gram-positive bacteria is greatly influenced by the microenvironment on the trans side of the cytoplasmic membrane, and secreted heterologous proteins are susceptible to rapid degradation by host cell proteases. In Bacillus subtilis, degradation occurs either as the proteins emerge from the presecretory translocase and prior to folding into their native conformation or after the native conformation has been reached. The former process generally involves membrane- and/or cell wall-bound proteases, while the latter involves proteases that are released into the culture medium. The identification and manipulation of factors that influence the folding of heterologous proteins has the potential to improve the yield of secreted heterologous proteins. Recombinant anthrax protective antigen (rPA) has been used as a model secreted heterologous protein because it is sensitive to proteolytic degradation both before and after folding into its native conformation. This paper describes the influence of the microenvironment on the trans side of the cytoplasmic membrane on the stability of rPA. Specifically, we have determined the influence of net cell wall charge and its modulation by the extent to which the anionic polymer teichoic acid is D-alanylated on the secretion and stability of rPA. The potential role of the dlt operon, responsible for D-alanylation, was investigated using a Bacillus subtilis strain encoding an inducible dlt operon. We show that, in the absence of D-alanylation, the yield of secreted rPA is increased 2.5-fold. The function of D-alanylation and the use of rPA as a model protein are evaluated with respect to the optimization of B. subtilis for the secretion of heterologous proteins. 相似文献
58.
L. G. Firbank 《Oecologia》1993,94(3):351-355
The changing populations of weeds during 13 years of the Broadbalk continuous wheat experiment were analysed to investigate the extent of differences in shortterm variability of cover between species. The data were from two sections of the experiment where winter wheat was grown continuously under herbicide treatment for 13 and 6 years respectively. Logistic regressions were fitted to the data. Equisetum arvense showed significant long-term increases on both sections; long-term trends were also detected in the longer data run for Agrostis stolonifera, Cirsium arvensa, Poa trivialis, Ranunculus arvensis and Vicia sativa, and for Medicago lupulina on the shorter data run. Variation around long-term trends was low in the case of Equisetum, and, in the longer data run, for Cirsium and Tussilago farfara, and high for Poa spp. and Vicia. Cover values on the two sections were positively correlated for Alopecurus myosuroides, Equisetum, Poa annua and Tripleurospermum inodorum. There was a weak correlation between C-S-R strategy and short-term variability; the more competitive species displayed less variability than the ruderal species. Furthermore, species regenerating from persistent seed banks were more variable in the short term than those regenerating from short-lived seed or bud banks. This can be explained by differences in response to year-to-year variation in environmental conditions, those species with persistent seed banks being typically more sensitive to annual fluctuations in the environment than those without. 相似文献
59.
Les Back 《Ethnic and racial studies》2013,36(5):849-853
60.