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81.
Efficient type-III secretion depends on cytosolic molecular chaperones, which bind specifically to the translocators and effectors. In the past there has been a tendency to shoe-horn all type-III-secretion chaperones into a single structural and functional class. However, we have shown that the LcrH/SycD-like chaperones consist of three central tetratricopeptide-like repeats that are predicted to fold into an all-alpha-helical array that is quite distinct from the known structure of the SycE class of chaperones. Furthermore, we predict that this array creates a peptide-binding groove that is utterly different from the helix-binding groove in SycE. We present a homology model of LcrH/SycD that is consistent with existing mutagenesis data. We also report the existence of tetratricopeptide-like repeats in regulators of type-III secretion, such as HilA from Salmonella enterica and HrpB from Ralstonia solanacearum. The discovery of tetratricopeptide-like repeats in type-III-secretion regulators and chaperones provides a new conceptual framework for structural and mutagenesis studies and signals a potential unification of prokaryotic and eukaryotic chaperone biology. 相似文献
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Nogo-A at CNS paranodes is a ligand of Caspr: possible regulation of K(+) channel localization 总被引:5,自引:0,他引:5
Nie DY Zhou ZH Ang BT Teng FY Xu G Xiang T Wang CY Zeng L Takeda Y Xu TL Ng YK Faivre-Sarrailh C Popko B Ling EA Schachner M Watanabe K Pallen CJ Tang BL Xiao ZC 《The EMBO journal》2003,22(21):5666-5678
We report Nogo-A as an oligodendroglial component congregating and interacting with the Caspr-F3 complex at paranodes. However, its receptor Nogo-66 receptor (NgR) does not segregate to specific axonal domains. CHO cells cotransfected with Caspr and F3, but not with F3 alone, bound specifically to substrates coated with Nogo-66 peptide and GST-Nogo-66. Binding persisted even after phosphatidylinositol- specific phospholipase C (PI-PLC) removal of GPI-linked F3 from the cell surface, suggesting a direct interaction between Nogo-66 and Caspr. Both Nogo-A and Caspr co-immunoprecipitated with Kv1.1 and Kv1.2, and the developmental expression pattern of both paralleled compared with Kv1.1, implicating a transient interaction between Nogo-A-Caspr and K(+) channels at early stages of myelination. In pathological models that display paranodal junctional defects (EAE rats, and Shiverer and CGT(-/-) mice), distances between the paired labeling of K(+) channels were shortened significantly and their localization shifted toward paranodes, while paranodal Nogo-A congregation was markedly reduced. Our results demonstrate that Nogo-A interacts in trans with axonal Caspr at CNS paranodes, an interaction that may have a role in modulating axon-glial junction architecture and possibly K(+)-channel localization during development. 相似文献
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Laboratory strains of Escherichia coli: model citizens or deceitful delinquents growing old disgracefully? 总被引:1,自引:0,他引:1
Escherichia coli stands unchallenged as biology's premier model organism. However, we propose, equipped with insights from the post-genomic era, a contrary view: that microbiology's chief idol has feet of clay. E. coli laboratory strains, particularly E. coli K-12, are far from model citizens, but instead degenerate and deceitful delinquents growing old disgracefully in our scientific institutions. E. coli K-12 is neither archetype nor ancestor. In addition, it has a far from optimal provenance for a model organism, with strong grounds for believing that current versions of the strain are quite distinct from any original wild-type free-living ancestor. In addition, it is usually studied under conditions far removed from its natural habitats and in ignorance of the selective pressures that have shaped its evolution. Fortunately, a flood of information from high-throughput genome sequencing, together with a new 'eco-evo' view of this model organism, promises to help put K-12 better into context. 相似文献
86.
The ETT2 gene cluster, encoding a second type III secretion system from Escherichia coli, is present in the majority of strains but has undergone widespread mutational attrition
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Ren CP Chaudhuri RR Fivian A Bailey CM Antonio M Barnes WM Pallen MJ 《Journal of bacteriology》2004,186(11):3547-3560
ETT2 is a second cryptic type III secretion system in Escherichia coli which was first discovered through the analysis of genome sequences of enterohemorrhagic E. coli O157:H7. Comparative analyses of Escherichia and Shigella genome sequences revealed that the ETT2 gene cluster is larger than was previously thought, encompassing homologues of genes from the Spi-1, Spi-2, and Spi-3 Salmonella pathogenicity islands. ETT2-associated genes, including regulators and chaperones, were found at the same chromosomal location in the majority of genome-sequenced strains, including the laboratory strain K-12. Using a PCR-based approach, we constructed a complete tiling path through the ETT2 gene cluster for 79 strains, including the well-characterized E. coli reference collection supplemented with additional pathotypes. The ETT2 gene cluster was found to be present in whole or in part in the majority of E. coli strains, whether pathogenic or commensal, with patterns of distribution and deletion mirroring the known phylogenetic structure of the species. In almost all strains, including enterohemorrhagic E. coli O157:H7, ETT2 has been subjected to varying degrees of mutational attrition that render it unable to encode a functioning secretion system. A second type III secretion system-associated locus that likely encodes the ETT2 translocation apparatus was found in some E. coli strains. Intact versions of both ETT2-related clusters are apparently present in enteroaggregative E. coli strain O42. 相似文献
87.
Pallen MJ 《Protein science : a publication of the Protein Society》2003,12(8):1804-1807
Phosphorylase kinase is a four-subunit enzyme involved in the regulation of glycogen breakdown. The traditional textbook view is that only the gamma subunit has enzymatic activity, whereas the other three subunits have a regulatory role. Evidence from homology searches and sequence alignments, however, shows that the alpha- and beta-subunits possess amino-terminal glucoamylase-like domains and suggests that they might possess a previously overlooked amylase activity. If true, this would have important implications for the understanding, diagnosis, and management of glycogen storage diseases. There is thus a clear need to test this hypothesis through enzymatic assays and structural studies. 相似文献
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