全文获取类型
收费全文 | 152篇 |
免费 | 37篇 |
出版年
2023年 | 1篇 |
2022年 | 2篇 |
2021年 | 1篇 |
2019年 | 2篇 |
2018年 | 2篇 |
2017年 | 1篇 |
2016年 | 4篇 |
2015年 | 8篇 |
2014年 | 7篇 |
2013年 | 9篇 |
2012年 | 5篇 |
2011年 | 12篇 |
2010年 | 12篇 |
2009年 | 6篇 |
2008年 | 6篇 |
2007年 | 9篇 |
2006年 | 6篇 |
2005年 | 5篇 |
2004年 | 11篇 |
2003年 | 8篇 |
2002年 | 10篇 |
2001年 | 3篇 |
2000年 | 8篇 |
1999年 | 13篇 |
1998年 | 6篇 |
1997年 | 3篇 |
1996年 | 4篇 |
1995年 | 1篇 |
1994年 | 1篇 |
1993年 | 1篇 |
1991年 | 1篇 |
1989年 | 1篇 |
1988年 | 3篇 |
1985年 | 1篇 |
1984年 | 1篇 |
1980年 | 1篇 |
1979年 | 2篇 |
1978年 | 2篇 |
1977年 | 2篇 |
1976年 | 1篇 |
1975年 | 3篇 |
1973年 | 2篇 |
1972年 | 1篇 |
1970年 | 1篇 |
排序方式: 共有189条查询结果,搜索用时 15 毫秒
91.
Marlène L.N. Dubuisson Bertrand de Wergifosse Pierre Kremers Jacqueline Marchand-Brynaert André Trouet Jean-François Rees 《Free radical research》2013,47(3):285-296
Coelenterazine (3,7-dihydro-2-(p-hydroxybenzyl)-6-(p-hydroxyphenyl)-8-benzylimidazolo[1,2-a]pyrazin-3-one) is a substrate for the bioluminescence reaction in many marine animals. Recent work showed that CLZn, its synthetic analogue CLZm, and their common oxidation product coelenteramine (CLM) have strong antioxidative properties in acellular lipid peroxidation systems as well as in rat hepatocytes subjected to tert-butyl hydroperoxide (t-BHP). Here, we analyzed the ability of CLZm and several imidazolopyrazinone (IMPZs) analogues to protect primary cultures of rat hepatocytes against a nitrofurantoin (NF)-induced oxidative stress. Comparison of protection capabilities with reference antioxidants yielded the following ranking: CLZm >>> BHT > Trolox C® > probucol > α-tocopherol. The comparison of CLZm with analogues lacking the phenol group in R1 revealed no differences although the presence of this phenol conferred superior protection against t-BHP. CLM, as well as its methoxylated analogue mCLM which lacks chain-breaking properties, were equally potent in preventing cellular damage caused by NF. mCLM and α-naphthoflavone, an inhibitor of cytochrome P450 (CYP450) IAI, similarly protected cells against NF-induced mortality and also equally inhibited EROD activity in methylcholanthrene-induced hepatocytes. The inhibition of EROD by CLZm and CLM was less pronounced. We suggest that the extent of protection conferred by IMPZs against NF-toxicity reflects both the occurrence of antioxidative properties detoxifying ROS produced within cells and inhibitory actions on CYP450 isoforms involved in the bioreduction of NF. 相似文献
92.
Lettuce‐produced hepatitis C virus E1E2 heterodimer triggers immune responses in mice and antibody production after oral vaccination
下载免费PDF全文
![点击此处可从《Plant biotechnology journal》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Jihong Liu Clarke Lisa Paruch Mihaela‐Olivia Dobrica Iuliana Caras Catalin Tucureanu Adrian Onu Sonya Ciulean Crina Stavaru Andre Eerde Yanliang Wang Hege Steen Sissel Haugslien Catalina Petrareanu Catalin Lazar Costin‐Ioan Popescu Ralph Bock Jean Dubuisson Norica Branza‐Nichita 《Plant biotechnology journal》2017,15(12):1611-1621
The hepatitis C virus (HCV) is a major etiologic agent for severe liver diseases (e.g. cirrhosis, fibrosis and hepatocellular carcinoma). Approximately 140 million people have chronic HCV infections and about 500 000 die yearly from HCV‐related liver pathologies. To date, there is no licensed vaccine available to prevent HCV infection and production of a HCV vaccine remains a major challenge. Here, we report the successful production of the HCV E1E2 heterodimer, an important vaccine candidate, in an edible crop (lettuce, Lactuca sativa) using Agrobacterium‐mediated transient expression technology. The wild‐type dimer (E1E2) and a variant without an N‐glycosylation site in the E2 polypeptide (E1E2?N6) were expressed, and appropriate N‐glycosylation pattern and functionality of the E1E2 dimers were demonstrated. The humoral immune response induced by the HCV proteins was investigated in mice following oral administration of lettuce antigens with or without previous intramuscular prime with the mammalian HEK293T cell‐expressed HCV dimer. Immunization by oral feeding only resulted in development of weak serum levels of anti‐HCV IgM for both antigens; however, the E1E2?N6 proteins produced higher amounts of secretory IgA, suggesting improved immunogenic properties of the N‐glycosylation mutant. The mice group receiving the intramuscular injection followed by two oral boosts with the lettuce E1E2 dimer developed a systemic but also a mucosal immune response, as demonstrated by the presence of anti‐HCV secretory IgA in faeces extracts. In summary, our study demonstrates the feasibility of producing complex viral antigens in lettuce, using plant transient expression technology, with great potential for future low‐cost oral vaccine development. 相似文献
93.
Rocha-Perugini V Montpellier C Delgrange D Wychowski C Helle F Pillez A Drobecq H Le Naour F Charrin S Levy S Rubinstein E Dubuisson J Cocquerel L 《PloS one》2008,3(4):e1866
Two to three percent of the world's population is chronically infected with hepatitis C virus (HCV) and thus at risk of developing liver cancer. Although precise mechanisms regulating HCV entry into hepatic cells are still unknown, several cell surface proteins have been identified as entry factors for this virus. Among these molecules, the tetraspanin CD81 is essential for HCV entry. Here, we have identified a partner of CD81, EWI-2wint, which is expressed in several cell lines but not in hepatocytes. Ectopic expression of EWI-2wint in a hepatoma cell line susceptible to HCV infection blocked viral entry by inhibiting the interaction between the HCV envelope glycoproteins and CD81. This finding suggests that, in addition to the presence of specific entry factors in the hepatocytes, the lack of a specific inhibitor can contribute to the hepatotropism of HCV. This is the first example of a pathogen gaining entry into host cells that lack a specific inhibitory factor. 相似文献
94.
Hepatitis C virus (HCV)-induced immunoglobulin hypermutation reduces the affinity and neutralizing activities of antibodies against HCV envelope protein
下载免费PDF全文
![点击此处可从《Journal of virology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Machida K Kondo Y Huang JY Chen YC Cheng KT Keck Z Foung S Dubuisson J Sung VM Lai MM 《Journal of virology》2008,82(13):6711-6720
Hepatitis C virus (HCV) often causes persistent infection despite the presence of neutralizing antibodies against the virus in the sera of hepatitis C patients. HCV infects both hepatocytes and B cells through the binding of its envelope glycoprotein E2 to CD81, the putative viral receptor. Previously, we have shown that E2-CD81 interaction induces hypermutation of heavy-chain immunoglobulin (V(H)) in B cells. We hypothesize that if HCV infects antibody-producing B cells, the resultant hypermutation of V(H) may lower the affinity and specificity of the HCV-specific antibodies, enabling HCV to escape from immune surveillance. To test this hypothesis, we infected human hybridoma clones producing either neutralizing or non-neutralizing anti-E2 or anti-E1 antibodies with a lymphotropic HCV (SB strain). All of the hybridoma clones, except for a neutralizing antibody-producing hybridoma, could be infected with HCV and support virus replication for at least 8 weeks after infection. The V(H) sequences in the infected hybridomas had a significantly higher mutation frequency than those in the uninfected hybridomas, with mutations concentrating in complementarity-determining region 3. These mutations lowered the antibody affinity against the targeting protein and also lowered the virus-neutralizing activity of anti-E2 antibodies. Furthermore, antibody-mediated complement-dependent cytotoxicity with the antibodies secreted from the HCV-infected hybridomas was impaired. These results suggest that HCV infection could cause some anti-HCV-antibody-producing hybridoma B cells to make less-protective antibodies. 相似文献
95.
The transmembrane domain of hepatitis C virus glycoprotein E1 is a signal for static retention in the endoplasmic reticulum 总被引:4,自引:0,他引:4
下载免费PDF全文
![点击此处可从《Journal of virology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Cocquerel L Duvet S Meunier JC Pillez A Cacan R Wychowski C Dubuisson J 《Journal of virology》1999,73(4):2641-2649
Hepatitis C virus (HCV) glycoproteins E1 and E2 assemble to form a noncovalent heterodimer which, in the cell, accumulates in the endoplasmic reticulum (ER). Contrary to what is observed for proteins with a KDEL or a KKXX ER-targeting signal, the ER localization of the HCV glycoprotein complex is due to a static retention in this compartment rather than to its retrieval from the cis-Golgi region. A static retention in the ER is also observed when E2 is expressed in the absence of E1 or for a chimeric protein containing the ectodomain of CD4 in fusion with the transmembrane domain (TMD) of E2. Although they do not exclude the presence of an intracellular localization signal in E1, these data do suggest that the TMD of E2 is an ER retention signal for HCV glycoprotein complex. In this study chimeric proteins containing the ectodomain of CD4 or CD8 fused to the C-terminal hydrophobic sequence of E1 were shown to be localized in the ER, indicating that the TMD of E1 is also a signal for ER localization. In addition, these chimeric proteins were not processed by Golgi enzymes, indicating that the TMD of E1 is responsible for true retention in the ER, without recycling through the Golgi apparatus. Together, these data suggest that at least two signals (TMDs of E1 and E2) are involved in ER retention of the HCV glycoprotein complex. 相似文献
96.
Topological changes in the transmembrane domains of hepatitis C virus envelope glycoproteins 总被引:8,自引:0,他引:8
Cocquerel L Op de Beeck A Lambot M Roussel J Delgrange D Pillez A Wychowski C Penin F Dubuisson J 《The EMBO journal》2002,21(12):2893-2902
Hepatitis C virus proteins are synthesized as a polyprotein cleaved by a signal peptidase and viral proteases. The behaviour of internal signal sequences at the C-terminus of the transmembrane domains of hepatitis C virus envelope proteins E1 and E2 is essential for the topology of downstream polypeptides. We determined the topology of these transmembrane domains before and after signal sequence cleavage by tagging E1 and E2 with epitopes and by analysing their accessibility in selectively permeabilized cells. We showed that, after cleavage by signal peptidase in the endoplasmic reticulum, the C-terminal orientation of these transmembrane domains changed from luminal to cytosolic. The dynamic behaviour of these transmembrane domains is unique and it is linked to their multifunctionality. By reorienting their C-terminus toward the cytosol and being part of a transmembrane domain, the signal sequences at the C-terminus of E1 and E2 contribute to new functions: (i) membrane anchoring; (ii) E1E2 heterodimerization; and (iii) endoplasmic reticulum retention. 相似文献
97.
98.
Glycosylation of hepatitis C virus envelope proteins 总被引:7,自引:0,他引:7
Enveloped viruses are surrounded by a membrane derived from the host-cell that contains proteins called "envelope proteins". These proteins play a major role in virus assembly and entry. In most of the enveloped viruses, they are modified by N-linked glycosylation which is supposed to play a role in their stability, antigenicity and biological functions. Glycosylation is also known to play a major role in the biogenesis of proteins by being directly and/or indirectly involved in protein folding. Recent studies on hepatitis C virus (HCV) envelope proteins have revealed a complex interplay between cleavage by signal peptidase, folding and glycosylation. The knowledge that has been accumulated on the early steps of glycosylation of these proteins is presented in this review. 相似文献
99.
Functional characterization of intracellular and secreted forms of a truncated hepatitis C virus E2 glycoprotein 总被引:13,自引:0,他引:13
下载免费PDF全文
![点击此处可从《Journal of virology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Flint M Dubuisson J Maidens C Harrop R Guile GR Borrow P McKeating JA 《Journal of virology》2000,74(2):702-709
The E2 protein of hepatitis C virus (HCV) is believed to be a virion surface glycoprotein that is a candidate for inclusion in an antiviral vaccine. A truncated soluble version of E2 has recently been shown to interact with CD81, suggesting that this protein may be a component of the receptor for HCV. When expressed in eukaryotic cells, a significant proportion of E2 forms misfolded aggregates. To analyze the specificity of interaction between E2 and CD81, the aggregated and monomeric forms of a truncated E2 glycoprotein (E2(661)) were separated by high-pressure liquid chromatography and analyzed for CD81 binding. Nonaggregated forms of E2 preferentially bound CD81 and a number of conformation-dependent monoclonal antibodies (MAbs). Furthermore, intracellular forms of E2(661) were found to bind CD81 with greater affinity than the extracellular forms. Intracellular and secreted forms of E2(661) were also found to differ in reactivity with MAbs and human sera, consistent with differences in antigenicity. Together, these data indicate that proper folding of E2 is important for its interaction with CD81 and that modifications of glycans can modulate this interaction. Identification of the biologically active forms of E2 will assist in the future design of vaccines to protect against HCV infection. 相似文献
100.
Dynamic interplay of membrane‐proximal POTRA domain and conserved loop L6 in Omp85 transporter FhaC
下载免费PDF全文
![点击此处可从《Molecular microbiology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Jeremy Guérin Nathalie Saint Catherine Baud Albano C. Meli Emilien Etienne Camille Locht Hervé Vezin Françoise Jacob‐Dubuisson 《Molecular microbiology》2015,98(3):490-501
Omp85 transporters mediate protein insertion into, or translocation across, membranes. They have a conserved architecture, with POTRA domains that interact with substrate proteins, a 16‐stranded transmembrane β barrel, and an extracellular loop, L6, folded back in the barrel pore. Here using electrophysiology, in vivo biochemical approaches and electron paramagnetic resonance, we show that the L6 loop of the Omp85 transporter FhaC changes conformation and modulates channel opening. Those conformational changes involve breaking the conserved interaction between the tip of L6 and the inner β‐barrel wall. The membrane‐proximal POTRA domain also exchanges between several conformations, and the binding of FHA displaces this equilibrium. We further demonstrate a dynamic, physical communication between the POTRA domains and L6, which must take place via the β barrel. Our findings thus link all three essential components of Omp85 transporters and indicate that they operate in a concerted fashion in the transport cycle. 相似文献