全文获取类型
收费全文 | 472篇 |
免费 | 44篇 |
出版年
2022年 | 6篇 |
2021年 | 4篇 |
2020年 | 5篇 |
2019年 | 2篇 |
2017年 | 5篇 |
2016年 | 9篇 |
2015年 | 15篇 |
2014年 | 13篇 |
2013年 | 21篇 |
2012年 | 22篇 |
2011年 | 25篇 |
2010年 | 12篇 |
2009年 | 16篇 |
2008年 | 18篇 |
2007年 | 14篇 |
2006年 | 17篇 |
2005年 | 15篇 |
2004年 | 16篇 |
2003年 | 13篇 |
2002年 | 17篇 |
2001年 | 12篇 |
2000年 | 18篇 |
1999年 | 16篇 |
1998年 | 12篇 |
1997年 | 12篇 |
1996年 | 3篇 |
1995年 | 3篇 |
1994年 | 13篇 |
1993年 | 4篇 |
1992年 | 21篇 |
1991年 | 18篇 |
1990年 | 14篇 |
1989年 | 15篇 |
1988年 | 4篇 |
1987年 | 10篇 |
1986年 | 9篇 |
1985年 | 7篇 |
1984年 | 12篇 |
1983年 | 5篇 |
1982年 | 5篇 |
1980年 | 3篇 |
1979年 | 5篇 |
1978年 | 3篇 |
1977年 | 3篇 |
1975年 | 2篇 |
1973年 | 3篇 |
1972年 | 3篇 |
1970年 | 2篇 |
1966年 | 3篇 |
1965年 | 3篇 |
排序方式: 共有516条查询结果,搜索用时 15 毫秒
221.
222.
223.
Reconstitution of alkaline-denatured catalase 总被引:2,自引:0,他引:2
224.
225.
226.
Detailed atomistic computer simulations are now widely used to study biological membranes, including increasingly mixed lipid systems that involve, for example, cholesterol, which is a key membrane lipid. Typically, simulations of these systems start from a preassembled bilayer because the timescale on which self-assembly occurs in mixed lipid systems is beyond the practical abilities of fully atomistic simulations. To overcome this limitation and study bilayer self-assembly, coarse-grained models have been developed. Although there are several coarse-grained models for cholesterol reported in the literature, these generally fail to account explicitly for the unique molecular features of cholesterol that relate to its function and role as a membrane lipid. In this work, we propose a new coarse-grained model for cholesterol that retains the molecule's unique features and, as a result, can be used to study crystalline structures of cholesterol. In the development of the model, two levels of coarse-graining are explored and the importance of retaining key molecular features in the coarse-grained model that are relevant to structural properties is investigated. 相似文献
227.
Beckham GT Bomble YJ Matthews JF Taylor CB Resch MG Yarbrough JM Decker SR Bu L Zhao X McCabe C Wohlert J Bergenstråhle M Brady JW Adney WS Himmel ME Crowley MF 《Biophysical journal》2010,99(11):3773-3781
Fungi and bacteria secrete glycoprotein cocktails to deconstruct cellulose. Cellulose-degrading enzymes (cellulases) are often modular, with catalytic domains for cellulose hydrolysis and carbohydrate-binding modules connected by linkers rich in serine and threonine with O-glycosylation. Few studies have probed the role that the linker and O-glycans play in catalysis. Since different expression and growth conditions produce different glycosylation patterns that affect enzyme activity, the structure-function relationships that glycosylation imparts to linkers are relevant for understanding cellulase mechanisms. Here, the linker of the Trichoderma reesei Family 7 cellobiohydrolase (Cel7A) is examined by simulation. Our results suggest that the Cel7A linker is an intrinsically disordered protein with and without glycosylation. Contrary to the predominant view, the O-glycosylation does not change the stiffness of the linker, as measured by the relative fluctuations in the end-to-end distance; rather, it provides a 16 Å extension, thus expanding the operating range of Cel7A. We explain observations from previous biochemical experiments in the light of results obtained here, and compare the Cel7A linker with linkers from other cellulases with sequence-based tools to predict disorder. This preliminary screen indicates that linkers from Family 7 enzymes from other genera and other cellulases within T. reesei may not be as disordered, warranting further study. 相似文献
228.
Brigida TL Lucena Billy M dos Santos João LS Moreira Ana Paula B Moreira Alvaro C Nunes Vasco Azevedo Anderson Miyoshi Fabiano L Thompson Marcos Antonio de MoraisJunior 《BMC microbiology》2010,10(1):298
Background
Bacteria may compete with yeast for nutrients during bioethanol production process, potentially causing economic losses. This is the first study aiming at the quantification and identification of Lactic Acid Bacteria (LAB) present in the bioethanol industrial processes in different distilleries of Brazil. 相似文献229.
McCabe C Samali A O'brien T 《Biochemical and biophysical research communications》2006,342(4):1240-1248
Cytokine-induced beta cell destruction may be mediated by the generation of nitric oxide and/or reactive oxygen species. The relative importance of NO and ROS in cytokine-induced beta cell pathophysiology remains unclear. This investigation evaluates and contrasts the cytoprotective potential of antioxidant gene transfer, versus NF-kappaB inhibition, using a degradation-resistant mutant of IkappaBalpha. NF-kappaB inhibition conferred significant protection against cytokine-induced damage whereas antioxidant overexpression failed to provide protection. Conferred cytoprotection was associated with a suppression of iNOS activation and nitrite accumulation. Our data implicates iNOS, as opposed to ROS, as the pivotal player in cytokine-induced beta cell damage. From a therapeutic standpoint, strategies aimed at targeting the activation of iNOS may harbor therapeutic potential in preserving beta cell survival in the face of proinflammatory cytokine exposure. 相似文献
230.
Dosage-sensitive sex reversal adrenal hypoplasia congenita critical region on the X chromosome, gene 1 (DAX1) (NR0B1), and small heterodimer partner (SHP) (NR0B2) are atypical nuclear receptor superfamily members that function primarily as corepressors through heterodimeric interactions with other nuclear receptors. Mutations in DAX1 cause adrenal hypoplasia congenita, and mutations in SHP lead to mild obesity and insulin resistance, but the mechanisms are unclear. We investigated the existence and subcellular localization of DAX1 and SHP homodimers and the dynamics of homodimerization. We demonstrated DAX1 homodimerization in the nucleus and cytoplasm, and dissociation of DAX1 homodimers upon heterodimerization with steroidogenic factor 1 (SF1) or ligand-activated estrogen receptor-alpha (ERalpha). DAX1 homodimerization involved an interaction between its amino and carboxy termini involving its LXXLL motifs and activation function (AF)-2 domain. We observed SHP homodimerization in the nucleus of mammalian cells and showed dissociation of SHP homodimers upon heterodimerization with ligand-activated ERalpha. We observed DAX1-SHP heterodimerization in the nucleus of mammalian cells and demonstrated the involvement of the LXXLL motifs and AF-2 domain of DAX1 in this interaction. We further demonstrate heterodimerization of DAX1 with its alternatively spliced isoform, DAX1A. This is the first evidence of homodimerization of individual members of the unusual NR0B nuclear receptor family and heterodimerization between its members. Our results suggest that DAX1 forms antiparallel homodimers through the LXXLL motifs and AF-2 domain. These homodimers may function as holding reservoirs in the absence of heterodimeric partners. The formation of DAX1 and SHP homodimers and DAX1-SHP and DAX1-DAX1A heterodimers suggests the possibility of novel functions independent of their coregulator roles, suggesting additional complexity in the molecular mechanisms of DAX1 and SHP action. 相似文献