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101.
102.
Angela B. Brueggemann Beth Mbesu Muroki Benard W. Kulohoma Angela Karani Eva Wanjiru Susan Morpeth Tatu Kamau Shahnaaz Sharif J. Anthony G. Scott 《PloS one》2013,8(11)
Background
The 10-valent pneumococcal conjugate vaccine (PCV10) was introduced in Kenya in 2011. Introduction of any PCV will perturb the existing pneumococcal population structure, thus the aim was to genotype pneumococci collected in Kilifi before PCV10.Methods and Findings
Using multilocus sequence typing (MLST), we genotyped >1100 invasive and carriage pneumococci from children, the largest collection genotyped from a single resource-poor country and reported to date. Serotype 1 was the most common serotype causing invasive disease and was rarely detected in carriage; all serotype 1 isolates were members of clonal complex (CC) 217. There were temporal fluctuations in the major circulating sequence types (STs); and although 1-3 major serotype 1, 14 or 23F STs co-circulated annually, the two major serotype 5 STs mainly circulated independently. Major STs/CCs also included isolates of serotypes 3, 12F, 18C and 19A and each shared ≤2 MLST alleles with STs that circulate widely elsewhere. Major CCs associated with non-PCV10 serotypes were predominantly represented by carriage isolates, although serotype 19A and 12F CCs were largely invasive and a serotype 10A CC was equally represented by invasive and carriage isolates.Conclusions
Understanding the pre-PCV10 population genetic structure in Kilifi will allow for the detection of changes in prevalence of the circulating genotypes and evidence for capsular switching post-vaccine implementation. 相似文献103.
104.
Two distinct patterns of immune recovery inflammatory syndrome (IRIS) are recognized, paradoxical and unmasking IRIS. Here we raise some concerns regarding the first case of neuroPCM-IRIS published to date, as recently proposed by Almeida and Roza (Mycopathologia 177:137–141, 2017) for a patient originally described by Silva-Vergara et al. (Mycopathologia 182:393–396, 2014), taking in account the different case definitions for IRIS and the cases of neuroparacoccidioidomycosis already described in the literature. We are concerned that data from the case report have been misinterpreted and that no regard has been given to the possibility that the development of manifestations of neuroPCM after starting antiretroviral therapy and antifungal treatments could represent the predicted course of a missed neuroPCM diagnosis at presentation whose treatment failed. We hypothesize that diagnosis of the neuroPCM would not have been missed if careful screening for opportunistic infection of the central nervous system was performed prior to antiretroviral therapy initiation. Currently, there is no definitive diagnostic test for IRIS and diagnostic suspicion, as well as its management, are based on image studies and non-specific clinical signs and symptoms of inflammation. IRIS remains a diagnosis of exclusion, after considering drug toxicity, microbiologic treatment failure and the expected course of newly or previously diagnosed opportunistic infections. 相似文献
105.
Julhiany de Fátima da Silva Juliana Vicentim Haroldo Cesar de Oliveira Caroline Maria Marcos Patricia Akemi Assato Patrícia Ferrari Andreotti Juliana Leal Monteiro da Silva Christiane Pienna Soares Gil Benard Ana Marisa Fusco Almeida Maria José Soares Mendes-Giannini 《Memórias do Instituto Oswaldo Cruz》2015,110(4):476-484
The fungal strain Paracoccidioides brasiliensis remains viable
inside of epithelial cells and can induce apoptosis in this population. However,
until now, the molecules that participate in this process remained unknown. Thus,
this study evaluated the contribution of two P. brasiliensis
molecules, the 14-3-3 and glycoprotein of 43 kDa proteins, which had been previously
described as extracellular matrix adhesins and apoptosis inductors in human
pneumocytes. Accordingly, epithelial cells were treated with these molecules for
different periods of time and the expression of the apoptosis regulating-proteins
Bak, Bax, Bcl-2, p53 and caspases were evaluated by terminal deoxynucleotidyl
transferase dUTP nick end labelling, flow cytometry and real-time polymerase chain
reaction analysis. Our results demonstrated that treatment with these molecules
induces apoptosis signalling in pulmonary epithelial cells, showing the same pattern
of programmed cell-death as that observed during infection with P.
brasiliensis. Thus, we could conclude that P.
brasiliensis uses these molecules as virulence factors that participate
not only in the fungal adhesion process to host cells, but also in other important
cellular mechanisms such as apoptosis. 相似文献
106.
Monteiro da Silva JL Andreotti PF Benard G Soares CP Miranda ET Mendes-Giannini MJ 《Antonie van Leeuwenhoek》2007,92(1):129-135
Paracoccidioidomycosis is caused by Paracoccidioides brasiliensis, which although not formally considered an intracellular pathogen, can be internalized by epithelial cells in vitro and in
vivo. The mechanisms used by P. brasiliensis to adhere to and invade non-professional phagocytes have not been identified. The signal-transduction networks, involving
protein tyrosine kinase (PTK) and protein phosphatase activities, can modulate crucial events during fungal infections. In
this study, the involvement of PTK has been investigated in P. brasiliensis adherence and invasion in mammalian epithelial cells. A significant inhibition of the fungal invasion occurred after the
pre-treatment of the epithelial cells with genistein, a specific tyrosine kinase inhibitor, indicating that the tyrosine kinase
pathway is involved in P. brasiliensis internalization. In contrast, when the fungus was treated, a slight (not significant) inhibition of PTK was observed, suggesting
that PTK might not be the fungus’ transduction signal pathway during the invasion process of epithelial cells. An intense
PTK immunofluorescence labeling was observed in the periphery of the P. brasiliensis infected cells, little PTK labeling was found in both uninfected cells and yeast cells, at later infection times (8 and 24 h).
Moreover, when the epithelial cells were treated with genistein and infected with P. brasiliensis, no labeling was observed, suggesting the importance of the PTK in the infectious process. These results suggest that PTK
pathway participates in the transduction signal during the initial events of the adhesion and invasion processes of P. brasiliensis to mammalian epithelial cells. 相似文献
107.
S. Benard J. Arnhold M. Lehnert J. Schiller K. Arnold 《Chemistry and physics of lipids》1999,100(1-2):115-125
As recently shown, different physiologically relevant lipid classes can easily be analyzed by matrix-assisted laser desorption and ionization time-of-flight mass spectrometry (MALDI–TOF MS). In the present study the first application of MALDI–TOF for the quantitative analysis of diacylglycerols is described. It is shown that the use of a suitable reference sample enables the quantification of diacylglycerols up to the picomolar range. The best reproducibility of quantitative results for diacylglycerols was obtained using a matrix of 2,5-dihydroxybenzoic acid in ethylacetate and incorporation of an internal standard of the same lipid class. A moderate laser power was used, resulting in a very low extent of fragmentation, allowing a quantification by using solely the highest signal arising from sodium adduct formation of diacylglycerols. A linear correlation between peak intensity and lipid concentration over one order of magnitude was found. The applicability of this new technique for the analysis of other lipids like phosphatidylcholines is also discussed. 相似文献
108.
Matrix-assisted laser desorption ionization and time-of-flight mass spectrometry (MALDI-TOF MS) has been used to investigate degradation products of two selected polysaccharides of cartilage (chondroitin sulfate and hyaluronic acid). Testicular hyaluronate lyase and chondroitin ABC lyase were used for enzymic digestion of both polysaccharides as well as of cartilage specimens. Polysaccharide solutions and cartilage supernatants were assayed by positive and negative MALDI-TOF MS. Especially chondroitin ABC lyase produced high amounts of digestion products (unsaturated di- and tetrasaccharides) from polysaccharides as well as from cartilage, clearly monitored by MALDI-TOF MS. It is concluded that MALDI-TOF MS provides a precise and fast tool for the determination of oligosaccharides since no previous derivatization is required. 相似文献
109.
Characterization of rac and cdc42 activation in chemoattractant-stimulated human neutrophils using a novel assay for active GTPases 总被引:28,自引:0,他引:28
A major function of Rac2 in neutrophils is the regulation of oxidant production important in bacterial killing. Rac and the related GTPase Cdc42 also regulate the dynamics of the actin cytoskeleton, necessary for leukocyte chemotaxis and phagocytosis of microorganisms. Although these GTPases appear to be critical downstream components of chemoattractant receptor signaling in human neutrophils, the pathways involved in direct control of Rac/Cdc42 activation remain to be determined. We describe an assay that measures the formation of Rac-GTP and Cdc42-GTP based on their specific binding to the p21-binding domain of p21-activated kinase 1. A p21-binding domain glutathione S-transferase fusion protein specifically binds Rac and Cdc42 in their GTP-bound forms both in vitro and in cell samples. Binding is selective for Rac and Cdc42 versus RhoA. Using this assay, we investigated Rac and Cdc42 activation in neutrophils and differentiated HL-60 cells. The chemoattractant fMet-Leu-Phe and the phorbol ester phorbol myristate acetate stimulate formation of Rac-GTP and Cdc42-GTP with distinct time courses that parallel cell activation. We also show that the signaling pathways leading to Rac and Cdc42 activation in HL-60 cells involve G proteins sensitive to pertussis toxin, as well as tyrosine kinase and phosphatidylinositol 3-kinase activities. 相似文献
110.
The ski7 antiviral protein is an EF1-alpha homolog that blocks expression of non-Poly(A) mRNA in Saccharomyces cerevisiae
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We mapped and cloned SKI7, a gene that negatively controls the copy number of L-A and M double-stranded RNA viruses in Saccharomyces cerevisiae. We found that it encodes a nonessential 747-residue protein with similarities to two translation factors, Hbs1p and EF1-alpha. The ski7 mutant was hypersensitive to hygromycin B, a result also suggesting a role in translation. The SKI7 product repressed the expression of nonpolyadenylated [non-poly(A)] mRNAs, whether capped or uncapped, thus explaining why Ski7p inhibits the propagation of the yeast viruses, whose mRNAs lack poly(A). The dependence of the Ski7p effect on 3' RNA structures motivated a study of the expression of capped non-poly(A) luciferase mRNAs containing 3' untranslated regions (3'UTRs) differing in length. In a wild-type strain, increasing the length of the 3'UTR increased luciferase expression due to both increased rates and duration of translation. Overexpression of Ski7p efficiently cured the satellite virus M2 due to a twofold-increased repression of non-poly(A) mRNA expression. Our experiments showed that Ski7p is part of the Ski2p-Ski3p-Ski8p antiviral system because a single ski7 mutation derepresses the expression of non-poly(A) mRNA as much as a quadruple ski2 ski3 ski7 ski8 mutation, and the effect of the overexpression of Ski7p is not obtained unless other SKI genes are functional. ski1/xrn1Delta ski2Delta and ski1/xrn1Delta ski7Delta mutants were viable but temperature sensitive for growth. 相似文献