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41.
Classical swine fever virus can remain virulent after specific elimination of the interferon regulatory factor 3-degrading function of Npro 总被引:1,自引:0,他引:1
Ruggli N Summerfield A Fiebach AR Guzylack-Piriou L Bauhofer O Lamm CG Waltersperger S Matsuno K Liu L Gerber M Choi KH Hofmann MA Sakoda Y Tratschin JD 《Journal of virology》2009,83(2):817-829
Pestiviruses prevent alpha/beta interferon (IFN-alpha/beta) production by promoting proteasomal degradation of interferon regulatory factor 3 (IRF3) by means of the viral N(pro) nonstructural protein. N(pro) is also an autoprotease, and its amino-terminal coding sequence is involved in translation initiation. We previously showed with classical swine fever virus (CSFV) that deletion of the entire N(pro) gene resulted in attenuation in pigs. In order to elaborate on the role of the N(pro)-mediated IRF3 degradation in classical swine fever pathogenesis, we searched for minimal amino acid substitutions in N(pro) that would specifically abrogate this function. Our mutational analyses showed that degradation of IRF3 and autoprotease activity are two independent but structurally overlapping functions of N(pro). We describe two mutations in N(pro) that eliminate N(pro)-mediated IRF3 degradation without affecting the autoprotease activity. We also show that the conserved standard sequence at these particular positions is essential for N(pro) to interact with IRF3. Surprisingly, when these two mutations are introduced independently in the backbones of highly and moderately virulent CSFV, the resulting viruses are not attenuated, or are only partially attenuated, in 8- to 10-week-old pigs. This contrasts with the fact that these mutant viruses have lost the capacity to degrade IRF3 and to prevent IFN-alpha/beta induction in porcine cell lines and monocyte-derived dendritic cells. Taken together, these results demonstrate that contrary to previous assumptions and to the case for other viral systems, impairment of IRF3-dependent IFN-alpha/beta induction is not a prerequisite for CSFV virulence. 相似文献
42.
Katiucia Batista Silva Paiva Willian Fernando Zambuzzi Thais Accorsi-Mendonça Rumio Taga Fabio Daumas Nunes Mari Cleide Sogayar José Mauro Granjeiro 《Journal of molecular histology》2009,40(3):201-207
Reversion-inducing-cysteine-rich protein with Kazal motifs (RECK) is a single membrane-anchored MMP-regulator and regulates
matrix metalloproteinases (MMP) 2, 9 and 14. In turn, MMPs are endopeptidases that play a pivotal role in remodeling ECM.
In this work, we decided to evaluate expression pattern of RECK in growing rat incisor during, specifically focusing out amelogenesis
process. Based on different kinds of ameloblasts, our results showed that RECK expression was conducted by secretory and post-secretory
ameloblasts. At the secretory phase, RECK was localized in the infra-nuclear region of the ameloblast, outer epithelium, near
blood vessels, and in the stellate reticulum. From the transition to the maturation phases, RECK was strongly expressed by
non-epithelial immuno-competent cells (macrophages and/or dendritic-like cells) in the papillary layer. From the transition
to the maturation stage, RECK expression was increased. RECK mRNA was amplified by RT-PCR from whole enamel organ. Here, we
verified the presence of RECK mRNA during all stages of amelogenesis. These events were governed by ameloblasts and by non-epithelial
cells residents in the enamel organ. Concluding, we found differential expression of MMPs-2, -9 and RECK in the different
phases of amelogenesis, suggesting that the tissue remodeling is rigorously controlled during dental mineralization. 相似文献
43.
Daniela Camargos Costa Ana Paula Madureira Lara Cotta Amaral Bruno Ant?nio Marinho Sanchez Luciano Teixeira Gomes Cor Jésus Fernandes Fontes Jean Ezequiel Limongi Cristiana Ferreira Alves de Brito Luzia Helena Carvalho 《Memórias do Instituto Oswaldo Cruz》2014,109(1):21-28
The polymerase chain reaction (PCR)-based methods for the diagnosis of malaria
infection are expected to accurately identify submicroscopic parasite carriers.
Although a significant number of PCR protocols have been described, few studies have
addressed the performance of PCR amplification in cases of field samples with
submicroscopic malaria infection. Here, the reproducibility of two well-established
PCR protocols (nested-PCR and real-time PCR for the Plasmodium 18
small subunit rRNA gene) were evaluated in a panel of 34 blood field samples from
individuals that are potential reservoirs of malaria infection, but were negative for
malaria by optical microscopy. Regardless of the PCR protocol, a large variation
between the PCR replicates was observed, leading to alternating positive and negative
results in 38% (13 out of 34) of the samples. These findings were quite different
from those obtained from the microscopy-positive patients or the unexposed
individuals; the diagnosis of these individuals could be confirmed based on the high
reproducibility and specificity of the PCR-based protocols. The limitation of PCR
amplification was restricted to the field samples with very low levels of
parasitaemia because titrations of the DNA templates were able to detect < 3
parasites/µL in the blood. In conclusion, conventional PCR protocols require careful
interpretation in cases of submicroscopic malaria infection, as inconsistent and
false-negative results can occur. 相似文献
44.
Reference methods for antifungal susceptibility tests recommend the use of conidia as inoculum. However, some isolates produce
few conidia, while the invasive form of filamentous fungi in general is hyphae making susceptibility tests infeaseble. These
facts suggest that other than conidia broth dilution method is required for susceptibility tests. The aim of this study was
to clarify if the hyphal growth inhibition rate could be used as a method of determining the antifungal susceptibility of
genus Microsporum. For this reason, a method which traces hyphal tips automatically and measures their growth rate was standardized for Microsporum spp. Control growth curves and test growth curves obtained by real-time observation of the hyphae groups responses to different
concentrations of terbinafine, griseofulvin, and ciclopiroxolamine were used to compare with minimum inhibitory concentrations
(MICs) obtained by conidia broth microdilution method. A visible reduction in the growth inhibition rate was observed when
hyphal activity was evaluated using the third or fourth serial two-fold dilution below the MIC determined by broth microdilution
for terbinafine and ciclopiroxolamine. For griseofulvin, this reduction occurred after the fifth dilution below the MIC. This
study highlights the importance of the inoculum type used to determine the in vitro susceptibility of Microsporum strains. We conclude that measurement of hyphal growth inhibition, despite being time consuming, could be a suitable method
for evaluating antifungal susceptibility, particularly for fungi as Microsporum spp. that produce a small (or not at all) number of conidia. 相似文献
45.
Cintia Ferreira Marinho Elzinandes Leal Azeredo Amanda Torrentes-Carvalho Alessandro Marins-Dos-Santos Claire Fernandes Kubelka Luiz José de Souza Rivaldo Venancio Cunha Luzia Maria de-Oliveira-Pinto 《PloS one》2014,9(7)
In dengue virus (DENV) infection, complement system (CS) activation appears to have protective and pathogenic effects. In severe dengue fever (DF), the levels of DENV non-structural-1 protein and of the products of complement activation, including C3a, C5a and SC5b-9, are higher before vascular leakage occurs, supporting the hypothesis that complement activation contributes to unfavourable outcomes. The clinical manifestations of DF range from asymptomatic to severe and even fatal. Here, we aimed to characterise CS by their receptors or activation product, in vivo in DF patients and in vitro by DENV-2 stimulation on monocytes. In comparison with healthy controls, DF patients showed lower expression of CR3 (CD11b), CR4 (CD11c) and, CD59 on monocytes. The DF patients who were high producers of SC5b-9 were also those that showed more pronounced bleeding or vascular leakage. Those findings encouraged us to investigate the role of CS in vitro, using monocytes isolated from healthy subjects. Prior blocking with CR3 alone (CD11b) or CR3 (CD11b/CD18) reduced viral infection, as quantified by the levels of intracellular viral antigen expression and soluble DENV non-structural viral protein. However, we found that CR3 alone (CD11b) or CR3 (CD11b/CD18) blocking did not influence major histocompatibility complex presentation neither active caspase-1 on monocytes, thus probably ruling out inflammasome-related mechanisms. Although it did impair the secretion of tumour necrosis factor alpha and interferon alpha. Our data provide strategies of blocking CR3 (CD11b) pathways could have implications for the treatment of viral infection by antiviral-related mechanisms. 相似文献
46.
47.
48.
André Fujita Jo?o Ricardo Sato Leonardo de Oliveira Rodrigues Carlos Eduardo Ferreira Cleide Mari Sogayar 《BMC bioinformatics》2006,7(1):469
Background
With the development of DNA hybridization microarray technologies, nowadays it is possible to simultaneously assess the expression levels of thousands to tens of thousands of genes. Quantitative comparison of microarrays uncovers distinct patterns of gene expression, which define different cellular phenotypes or cellular responses to drugs. Due to technical biases, normalization of the intensity levels is a pre-requisite to performing further statistical analyses. Therefore, choosing a suitable approach for normalization can be critical, deserving judicious consideration. 相似文献49.
Cavada BS da Silva LI Ramos MV Galvani FR Grangeiro TB Leite KB Assreuy AM Cajazeiras JB Calvete JJ 《Protein and peptide letters》2003,10(6):607-617
A glucose/mannose lectin was purified by affinity chromatography from Pisum arvense seeds (PAL) and the 50 kDa molecular mass in solution determined by size exclusion chromatography. SDS-PAGE and electrospray ionization mass spectrometry showed two distinct polypeptide chains: alpha (Mr. 5591 Da) and beta (19986 Da). The lectin was extensively characterized in terms of its biochemical and biological aspects. The amino acid sequence was established by Edman degradation of overlapping peptides. PAL in solution behaves as a dimer and has its monomeric structure formed by two distinct polypeptide chains named alpha (Mr. 5591 Da) and beta (19986 Da) by Electrospray ionization (ESI) mass spectrometry. PAL possesses identical amino acid sequences to that of pea seed lectin but undoubtedly does not exhibit sequence heterogeneity. It is discussed that P. arvense should be considered as a synonym of P. sativum. Furthermore, like pea lectin, PAL discriminates biantennary fucosylated glycan, determined by surface plasmon resonance. 相似文献
50.
Michelle H. F. Dias Luiz F. F. Guimares Matheus G. Barcelos Eduardo U. M. Moreira Maria F. A. do Nascimento Taís N. de Souza Camilla V. Pires Talita A. F. Monteiro Jaap M. Middeldorp Irene S. Soares Cor J. F. Fontes Francis B. Ntumngia John H. Adams Flora S. Kano Luzia H. Carvalho 《PLoS neglected tropical diseases》2022,16(8)
BackgroundThe simultaneous infection of Plasmodium falciparum and Epstein-Barr virus (EBV) could promote the development of the aggressive endemic Burkitt’s Lymphoma (eBL) in children living in P. falciparum holoendemic areas. While it is well-established that eBL is not related to other human malaria parasites, the impact of EBV infection on the generation of human malaria immunity remains largely unexplored. Considering that this highly prevalent herpesvirus establishes a lifelong persistent infection on B-cells with possible influence on malaria immunity, we hypothesized that EBV co-infection could have impact on the naturally acquired antibody responses to P. vivax, the most widespread human malaria parasite.Methodology/Principal findingsThe study design involved three cross-sectional surveys at six-month intervals (baseline, 6 and 12 months) among long-term P. vivax exposed individuals living in the Amazon rainforest. The approach focused on a group of malaria-exposed individuals whose EBV-DNA (amplification of balf-5 gene) was persistently detected in the peripheral blood (PersVDNA, n = 27), and an age-matched malaria-exposed group whose EBV-DNA could never be detected during the follow-up (NegVDNA, n = 29). During the follow-up period, the serological detection of EBV antibodies to lytic/ latent viral antigens showed that IgG antibodies to viral capsid antigen (VCA-p18) were significantly different between groups (PersVDNA > NegVDNA). A panel of blood-stage P. vivax antigens covering a wide range of immunogenicity confirmed that in general PersVDNA group showed low levels of antibodies as compared with NegVDNA. Interestingly, more significant differences were observed to a novel DBPII immunogen, named DEKnull-2, which has been associated with long-term neutralizing antibody response. Differences between groups were less pronounced with blood-stage antigens (such as MSP1-19) whose levels can fluctuate according to malaria transmission.Conclusions/SignificanceIn a proof-of-concept study we provide evidence that a persistent detection of EBV-DNA in peripheral blood of adults in a P. vivax semi-immune population may impact the long-term immune response to major malaria vaccine candidates. 相似文献