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排序方式: 共有147条查询结果,搜索用时 296 毫秒
1.
Mapping of mutations contributing to the temperature sensitivity of the Sabin 1 vaccine strain of poliovirus. 总被引:8,自引:4,他引:4
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M M Georgescu M Tardy-Panit S Guillot R Crainic F Delpeyroux 《Journal of virology》1995,69(9):5278-5286
The temperature-sensitive and attenuated phenotypes of the Sabin type 1 vaccine strain of poliovirus result from numerous point mutations which occurred in the virulent Mahoney virus parent. One of these mutations is located in a 3D polymerase (3Dpol) codon (U-6203-->C, Tyr-73-->His) and is involved in attenuation in common mice (M. Tardy-Panit, B. Blondel, A. Martin, F. Tekaia, F. Horaud, and F. Delpeyroux, J. Virol. 67:4630-4638, 1993). This mutation also appears to contribute to temperature sensitivity, in association with at least 1 other of the 10 mutations of the 3'-terminal part of the genome including the 3Dpol coding and 3' noncoding regions. To map the other mutation(s), we constructed poliovirus mutants by mutagenesis and recombination of Mahoney and Sabin 1 cDNAs. Characterization of these poliovirus mutants showed that a second mutation in a 3Dpol codon (C-7071-->U, Thr-362-->Ile) contributes to temperature sensitivity. A mutation in the 3' noncoding region of the genome (A-7441-->G), alone or linked to another mutation (U-7410-->C), also appeared to be involved in this phenotype. The temperature-sensitive effect associated with the 3'-terminal part of the Sabin 1 genome results from the cumulative and/or synergistic effects of at least three genetic determinants, i.e., the His-73 and Ile-362 codons of 3Dpol and nucleotide G-7441. Sequence analysis of strains isolated from patients with vaccine-associated paralytic poliomyelitis showed that these genetic determinants are selected against in vivo, although the Ile-362 codon appeared to be more stable than either the His-73 codon or G-7441. These genetic determinants may contribute to the safety of Sabin 1 in vaccines. 相似文献
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3.
The beta-propensity of Tau determines aggregation and synaptic loss in inducible mouse models of tauopathy 总被引:1,自引:0,他引:1
Eckermann K Mocanu MM Khlistunova I Biernat J Nissen A Hofmann A Schönig K Bujard H Haemisch A Mandelkow E Zhou L Rune G Mandelkow EM 《The Journal of biological chemistry》2007,282(43):31755-31765
Neurofibrillary lesions are characteristic for a group of human diseases, named tauopathies, which are characterized by prominent intracellular accumulations of abnormal filaments formed by the microtubule-associated protein Tau. The tauopathies are accompanied by abnormal changes in Tau protein, including pathological conformation, somatodendritic mislocalization, hyperphosphorylation, and aggregation, whose interdependence is not well understood. To address these issues we have created transgenic mouse lines in which different variants of full-length Tau are expressed in a regulatable fashion, allowing one to switch the expression on and off at defined time points. The Tau variants differ by small mutations in the hexapeptide motifs that control the ability of Tau to adopt a beta-structure conformation and hence to aggregate. The "pro-aggregation" mutant DeltaK280, derived from one of the mutations observed in frontotemporal dementias, aggregates avidly in vitro, whereas the "anti-aggregation" mutant DeltaK280/PP cannot aggregate because of two beta-breaking prolines. In the transgenic mice, the pro-aggregation Tau induces a pathological conformation and pre-tangle aggregation, even at low expression levels, the anti-aggregation mutant does not. This illustrates that abnormal aggregation is primarily controlled by the molecular structure of Tau in vitro and in the organism. Both variants of Tau become mislocalized and hyperphosphorylated independently of aggregation, suggesting that localization and phosphorylation are mainly a consequence of increased concentration. These pathological changes are reversible when the expression of Tau is switched off. The pro-aggregation Tau causes a strong reduction in spine synapses. 相似文献
4.
5.
Backbone dynamics of green fluorescent protein and the effect of histidine 148 substitution 总被引:2,自引:0,他引:2
Seifert MH Georgescu J Ksiazek D Smialowski P Rehm T Steipe B Holak TA 《Biochemistry》2003,42(9):2500-2512
Green fluorescent protein (GFP) and its mutants have become valuable tools in molecular biology. GFP has been regarded as a very stable and rigid protein with the beta-barrel shielding the chromophore from the solvent. Here, we report the 15N nuclear magnetic resonance (NMR) studies on the green fluorescent protein (GFPuv) and its mutant His148Gly. 15N NMR relaxation studies of GFPuv show that most of the beta-barrel of GFP is rigid on the picosecond to nanosecond time scale. For several regions, including the first alpha-helix and beta-sheets 3, 7, 8, and 10, increased hydrogen-deuterium exchange rates suggest a substantial conformational flexibility on the microsecond to millisecond time scales. Mutation of residue 148 located in beta-sheet 7 is known to have a strong impact on the fluorescence properties of GFPs. UV absorption and fluorescence spectra in combination with 1H-15N NMR spectra indicate that the His148Gly mutation not only reduces the absorption of the anionic chromophore state but also affects the conformational stability, leading to the appearance of doubled backbone amide resonances for a number of residues. This suggests the presence of two conformations in slow exchange on the NMR time scale in this mutant. 相似文献
6.
Structure of a sliding clamp on DNA 总被引:4,自引:0,他引:4
The structure of the E. coli beta clamp polymerase processivity factor has been solved in complex with primed DNA. Interestingly, the clamp directly binds the DNA duplex and also forms a crystal contact with the ssDNA template strand, which binds into the protein-binding pocket of the clamp. We demonstrate that these clamp-DNA interactions function in clamp loading, perhaps by inducing the ring to close around DNA. Clamp binding to template ssDNA may also serve to hold the clamp at a primed site after loading or during switching of multiple factors on the clamp. Remarkably, the DNA is highly tilted as it passes through the beta ring. The pronounced 22 degrees angle of DNA through beta may enable DNA to switch between multiple factors bound to a single clamp simply by alternating from one protomer of the ring to the other. 相似文献
7.
From a practical point of view, the most efficient strategy for pest control is to combine an array of techniques to control the wide variety of potential pests that may threaten crops in an approach known as integrated pest management (IPM). In this paper, we propose a predator-prey (pest) model of IPM in which pests are impulsively controlled by means of spraying pesticides (the chemical control) and releasing natural predators (the biological control). It is assumed that the biological and chemical control are used with the same periodicity, but not simultaneously. The functional response of the predator is allowed to be predator-dependent, in the form of a Beddington-DeAngelis functional response, rather than to have a perhaps more classical prey-only dependence. The local and global stability of the pest-eradication periodic solution, as well as the permanence of the system, are obtained under integral conditions which are shown to have biological significance. In a certain limiting case, it is shown that a nontrivial periodic solution emerges via a supercritical bifurcation. Finally, our findings are confirmed by means of numerical simulations. 相似文献
8.
Genetic Variability of Yersinia pestis Isolates as Predicted by PCR-Based IS100 Genotyping and Analysis of Structural Genes Encoding Glycerol-3-Phosphate Dehydrogenase (glpD) 总被引:3,自引:0,他引:3
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Vladimir L. Motin Anca M. Georgescu Jeffrey M. Elliott Ping Hu Patricia L. Worsham Linda L. Ott Tomas R. Slezak Bahrad A. Sokhansanj Warren M. Regala Robert R. Brubaker Emilio Garcia 《Journal of bacteriology》2002,184(4):1019-1027
A PCR-based genotyping system that detects divergence of IS100 locations within the Yersinia pestis genome was used to characterize a large collection of isolates of different biovars and geographical origins. Using sequences derived from the glycerol-negative biovar orientalis strain CO92, a set of 27 locus-specific primers was designed to amplify fragments between the end of IS100 and its neighboring gene. Geographically diverse members of the orientalis biovar formed a homogeneous group with identical genotype with the exception of strains isolated in Indochina. In contrast, strains belonging to the glycerol-positive biovar antiqua showed a variety of fingerprinting profiles. Moreover, strains of the biovar medievalis (also glycerol positive) clustered together with the antiqua isolates originated from Southeast Asia, suggesting their close phylogenetic relationships. Interestingly, a Manchurian biovar antiqua strain Nicholisk 51 displayed a genotyping pattern typical of biovar orientalis isolates. Analysis of the glycerol pathway in Y. pestis suggested that a 93-bp deletion within the glpD gene encoding aerobic glycerol-3-phosphate dehydrogenase might account for the glycerol-negative phenotype of the orientalis biovar. The glpD gene of strain Nicholisk 51 did not possess this deletion, although it contained two nucleotide substitutions characteristic of the glpD version found exclusively in biovar orientalis strains. To account for this close relationship between biovar orientalis strains and the antiqua Nicholisk 51 isolate, we postulate that the latter represents a variant of this biovar with restored ability to ferment glycerol. The fact that such a genetic lesion might be repaired as part of the natural evolutionary process suggests the existence of genetic exchange between different Yersinia strains in nature. The relevance of this observation on the emergence of epidemic Y. pestis strains is discussed. 相似文献
9.
The benign chondroblastoma is rarely located at the leg and hand bones. The reported case had a deformation of the first phalanx of the left leg second finger, clinico-radiologically diagnosed as a chondroma, and only the histopathological examination sets the diagnosis of benign chondroblastoma. 相似文献
10.
C.T. Dragomir D.T. Stefnescu I. Georgescu G.N. Stere L. Ciuca D. Ungureanu F. Tudor R. Chirvasie 《生物化学与生物物理学报:生物膜》1975,389(3):530-540
Xenon passage across the erythrocyte membrane was investigated by performing several types of tests. The effects of some enzyme inhibitors (ouabain, NaF, dinitrophenol, low temperature), representing various modifications of the mentioned transport phenomenon, led to the conclusion of the existence of a strong correlation between the cellular energetic metabolism (and, hence, the energy supply for membrane processes) and the xenon accumulation into the erythrocyte. The experimental data obtained indicate that the xenon concentration in the cell water exceeds the concentration in the incubation solution by about 20 %. The metabolic inhibitors practically equalise the xenon concentrations in the cell water and in the surrounding medium. The possible theoretical consequences of these facts are taken into account and analysed. 相似文献