全文获取类型
收费全文 | 185篇 |
免费 | 16篇 |
出版年
2023年 | 1篇 |
2022年 | 3篇 |
2021年 | 8篇 |
2020年 | 3篇 |
2019年 | 3篇 |
2018年 | 4篇 |
2017年 | 7篇 |
2016年 | 10篇 |
2015年 | 14篇 |
2014年 | 12篇 |
2013年 | 12篇 |
2012年 | 17篇 |
2011年 | 20篇 |
2010年 | 7篇 |
2009年 | 10篇 |
2008年 | 14篇 |
2007年 | 8篇 |
2006年 | 5篇 |
2005年 | 5篇 |
2004年 | 5篇 |
2003年 | 5篇 |
2002年 | 4篇 |
2001年 | 3篇 |
1997年 | 1篇 |
1996年 | 4篇 |
1993年 | 2篇 |
1991年 | 1篇 |
1989年 | 2篇 |
1986年 | 2篇 |
1985年 | 1篇 |
1983年 | 1篇 |
1982年 | 2篇 |
1978年 | 1篇 |
1973年 | 1篇 |
1972年 | 1篇 |
1965年 | 1篇 |
1963年 | 1篇 |
排序方式: 共有201条查询结果,搜索用时 31 毫秒
21.
The SMN complex 总被引:7,自引:0,他引:7
The survival of motor neurons (SMN) protein is the product of the disease-determining gene of the neurodegenerative disorder spinal muscular atrophy (SMA). SMN is part of a stable multiprotein complex that is found in all metazoan cells in the cytoplasm and in nuclear Gems. The SMN complex contains, in addition to SMN, at least six other proteins, named Gemins2-7, and plays an essential role in the assembly of the spliceosomal small nuclear ribonucleoproteins (snRNPs). Through its binding to specific sequences in the snRNAs, the SMN complex surveys the correct identity of the target RNAs and facilitates snRNP assembly. Based on its ability to interact with several other protein and RNA components of cellular RNPs, it is likely that the SMN complex functions as an assemblyosome in the formation of diverse RNP particles, some of which may be of particular importance to the motor neuron. A detailed understanding of the cellular roles of the SMN complex may help the development of therapeutic strategies for this neurodegenerative disease. 相似文献
22.
23.
Jorge Reyes-del Valle Cynthia de la Fuente Mallory A. Turner Christoph Springfeld Swapna Apte-Sengupta Marie E. Frenzke Amelie Forest Jillian Whidby Joseph Marcotrigiano Charles M. Rice Roberto Cattaneo 《Journal of virology》2012,86(21):11558-11566
Hepatitis C virus (HCV) infection remains a serious public health problem worldwide. Treatments are limited, and no preventive vaccine is available. Toward developing an HCV vaccine, we engineered two recombinant measles viruses (MVs) expressing structural proteins from the prototypic HCV subtype 1a strain H77. One virus directs the synthesis of the HCV capsid (C) protein and envelope glycoproteins (E1 and E2), which fold properly and form a heterodimer. The other virus expresses the E1 and E2 glycoproteins separately, with each one fused to the cytoplasmic tail of the MV fusion protein. Although these hybrid glycoproteins were transported to the plasma membrane, they were not incorporated into MV particles. Immunization of MV-susceptible, genetically modified mice with either vector induced neutralizing antibodies to MV and HCV. A boost with soluble E2 protein enhanced titers of neutralizing antibody against the homologous HCV envelope. In animals primed with MV expressing properly folded HCV C-E1-E2, boosting also induced cross-neutralizating antibodies against two heterologous HCV strains. These results show that recombinant MVs retain the ability to induce MV-specific humoral immunity while also eliciting HCV neutralizing antibodies, and that anti-HCV immunity can be boosted with a single dose of purified E2 protein. The use of MV vectors could have advantages for pediatric HCV vaccination. 相似文献
24.
25.
A Croset L Delafosse JP Gaudry C Arod L Glez C Losberger D Begue A Krstanovic F Robert F Vilbois L Chevalet B Antonsson 《Journal of biotechnology》2012,161(3):336-348
Glycosylation is one of the most common posttranslational modifications of proteins. It has important roles for protein structure, stability and functions. In vivo the glycostructures influence pharmacokinetics and immunogenecity. It is well known that significant differences in glycosylation and glycostructures exist between recombinant proteins expressed in mammalian, yeast and insect cells. However, differences in protein glycosylation between different mammalian cell lines are much less well known. In order to examine differences in glycosylation in mammalian cells we have expressed 12 proteins in the two commonly used cell lines HEK and CHO. The cells were transiently transfected, and the expressed proteins were purified. To identify differences in glycosylation the proteins were analyzed on SDS-PAGE, isoelectric focusing (IEF), mass spectrometry and released glycans on capillary gel electrophoresis (CGE-LIF). For all proteins significant differences in the glycosylation were detected. The proteins migrated differently on SDS-PAGE, had different isoform patterns on IEF, showed different mass peak distributions on mass spectrometry and showed differences in the glycostructures detected in CGE. In order to verify that differences detected were attributed to glycosylation the proteins were treated with deglycosylating enzymes. Although, culture conditions induced minor changes in the glycosylation the major differences were between the two cell lines. 相似文献
26.
27.
28.
29.
Most biological processes are regulated through complex networks of transient protein interactions where a globular domain in one protein recognizes a linear peptide from another, creating a relatively small contact interface. Although sufficient to ensure binding, these linear motifs alone are usually too short to achieve the high specificity observed, and additional contacts are often encoded in the residues surrounding the motif (i.e. the context). Here, we systematically identified all instances of peptide-mediated protein interactions of known three-dimensional structure and used them to investigate the individual contribution of motif and context to the global binding energy. We found that, on average, the context is responsible for roughly 20% of the binding and plays a crucial role in determining interaction specificity, by either improving the affinity with the native partner or impeding non-native interactions. We also studied and quantified the topological and energetic variability of interaction interfaces, finding a much higher heterogeneity in the context residues than in the consensus binding motifs. Our analysis partially reveals the molecular mechanisms responsible for the dynamic nature of peptide-mediated interactions, and suggests a global evolutionary mechanism to maximise the binding specificity. Finally, we investigated the viability of non-native interactions and highlight cases of potential cross-reaction that might compensate for individual protein failure and establish backup circuits to increase the robustness of cell networks. 相似文献