全文获取类型
收费全文 | 506682篇 |
免费 | 167460篇 |
国内免费 | 29829篇 |
专业分类
703971篇 |
出版年
2018年 | 6101篇 |
2017年 | 5576篇 |
2016年 | 7624篇 |
2015年 | 10481篇 |
2014年 | 11533篇 |
2013年 | 15177篇 |
2012年 | 17463篇 |
2011年 | 18013篇 |
2010年 | 14160篇 |
2009年 | 17951篇 |
2008年 | 16700篇 |
2007年 | 17041篇 |
2006年 | 14694篇 |
2005年 | 14537篇 |
2004年 | 14283篇 |
2003年 | 13291篇 |
2002年 | 13502篇 |
2001年 | 25374篇 |
2000年 | 23484篇 |
1999年 | 23042篇 |
1998年 | 13610篇 |
1997年 | 13478篇 |
1996年 | 12777篇 |
1995年 | 12595篇 |
1994年 | 12071篇 |
1993年 | 11593篇 |
1992年 | 19728篇 |
1991年 | 18946篇 |
1990年 | 19249篇 |
1989年 | 18550篇 |
1988年 | 16719篇 |
1987年 | 15650篇 |
1986年 | 14384篇 |
1985年 | 13833篇 |
1984年 | 11363篇 |
1983年 | 9624篇 |
1982年 | 8399篇 |
1981年 | 7572篇 |
1980年 | 7206篇 |
1979年 | 10334篇 |
1978年 | 8348篇 |
1977年 | 7804篇 |
1976年 | 7255篇 |
1975年 | 7225篇 |
1974年 | 7914篇 |
1973年 | 7789篇 |
1972年 | 7460篇 |
1971年 | 6901篇 |
1970年 | 5913篇 |
1969年 | 5869篇 |
排序方式: 共有10000条查询结果,搜索用时 10 毫秒
41.
Protein Kinase PKR Mediates the Apoptosis Induction and Growth Restriction Phenotypes of C Protein-Deficient Measles Virus 总被引:1,自引:0,他引:1
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)
Ann M. Toth Patricia Devaux Roberto Cattaneo Charles E. Samuel 《Journal of virology》2009,83(2):961-968
The measles virus (MV) accessory proteins V and C play important roles in MV replication and pathogenesis. Infection with recombinant MV lacking either V or C causes more cell death than infection with the parental vaccine-equivalent virus (MVvac), and C-deficient virus grows poorly relative to the parental virus. Here, we show that a major effector of the C phenotype is the RNA-dependent protein kinase PKR. Using human HeLa cells stably deficient in PKR as a result of RNA interference-mediated knockdown (PKRkd cells), we demonstrated that a reduction in PKR partially rescued the growth defect of C knockout (Cko) virus but had no effect on the growth of either wild-type (WT) or V knockout (Vko) virus. Increased growth of the Cko virus in PKRkd cells correlated with increased viral protein expression, while defective growth and decreased protein expression in PKR-sufficient cells correlated with increased phosphorylation of PKR and the α subunit of eukaryotic initiation factor 2. Furthermore, infection with WT, Vko, or especially Cko virus caused significantly less apoptosis in PKRkd cells than in PKR-sufficient cells. Although apoptosis induced by Cko virus infection in PKR-sufficient cells was blocked by a caspase antagonist, the growth of Cko virus was not restored to the WT level by treatment with this pharmacologic inhibitor. Taken together, these results indicate that PKR plays an important antiviral role during MV infection but that the virus growth restriction by PKR is not dependent upon the induction of apoptosis. Furthermore, the results establish that a principal function of the MV C protein is to antagonize the proapoptotic and antiviral activities of PKR. 相似文献
42.
Formation of rings from Drosophila DNA fragments 总被引:1,自引:0,他引:1
43.
Four myeloid cell lines (M1, WEHI-3B D+, FDC-P1, and 32D) were screened for the presence of J11d antigen. One of these cell lines, the myeloid leukemia M1, was found to express a high level of J11d antigen on the cell surface. Recombinant mouse leukemic inhibitory factor (rm-LIF), recombinant human LIF (rh-LIF), and steroids (hydrocortisone and dexamethasone) could induce M1 cells to undergo monocytic differentiation. The level of J11d antigen was greatly reduced after treatment of the cells with LIF or steroids. Western blotting revealed that the apparent molecular weight of the J11d antigen on M1 cells was 45-48 kDa. Furthermore, the level of J11d mRNA was also reduced during LIF-induced differentiation of M1 cells. 相似文献
44.
45.
46.
Markers for trans-Golgi Membranes and the Intermediate Compartment Localize to Induced Membranes with Distinct Replication Functions in Flavivirus-Infected Cells
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)
Replication of the flavivirus Kunjin virus is associated with virus-induced membrane structures within the cytoplasm of infected cells; these membranes appear as packets of vesicles associated with the sites of viral RNA synthesis and as convoluted membranes (CM) and paracrystalline arrays (PC) containing the components of the virus-specified protease (E. G. Westaway, J. M. Mackenzie, M. T. Kenney, M. K. Jones, and A. A. Khromykh, J. Virol. 71:6650-6661, 1997). To determine the cellular origins of these membrane structures, we compared the immunolabelling patterns of several cell markers in relation to these sites by immunofluorescence and immunoelectron microscopy. A marker for the trans-Golgi membranes and the trans-Golgi network, 1,4-galactosyltransferase (GalT), was redistributed to large foci in the cytoplasm of Kunjin virus-infected cells, partially coincident with immunofluorescent foci associated with the putative sites of viral RNA synthesis. As determined by immunoelectron microscopy, the induced vesicle packets contained GalT, whereas the CM and PC contained a specific protein marker for the intermediate compartment (ERGIC53). A further indicator of the role of cellular organelles in their biogenesis was the observation that the Golgi apparatus-disrupting agent brefeldin A prevented further development of immunofluorescent foci of induced membranes if added before the end of the latent period but that once formed, these membrane foci were resistant to brefeldin A dispersion. Reticulum membranes emanating from the induced CM and PC were also labelled with the rough endoplasmic reticulum marker anti-protein disulfide isomerase and were obviously redistributed during infection. This is the first report identifying trans-Golgi membranes and the intermediate compartment as the apparent sources of the flavivirus-induced membranes involved in events of replication. 相似文献
47.
The way a protein responds to mutation provides key insights into its architecture and energetics. Mutations are improving the understanding both of protein folding and stability, and of the adaptability of the hydrophobic core. The importance of intermolecular effects in crystal structures is being emphasized and new insights into the correspondence between crystal and solution structures are being developed. 相似文献
48.
The goal of this study was to develop a new implantable transducer for measuring anterior cruciate ligament (ACL) graft tension postoperatively in patients who have undergone ACL reconstructive surgery. A unique approach was taken of integrating the transducer into a femoral fixation device. To devise a practical in vivo calibration protocol for the fixation device transducer (FDT), several hypotheses were investigated: (1) The use of a cable versus the actual graft as the means for applying load to the FDT during calibration has no significant effect on the accuracy of the FDT tension measurements; (2) the number of flexion angles at which the device is calibrated has no significant effect on the accuracy of the FDT measurements; (3) the friction between the graft and femoral tunnel has no significant effect on measurement accuracy. To provide data for testing these hypotheses, the FDT was first calibrated with both a cable and a graft over the full range of flexion. Then graft tension was measured simultaneously with both the FDT on the femoral side and load cells, which were connected to the graft on the tibial side, as five cadaver knees were loaded externally. Measurements were made with both standard and overdrilled tunnels. The error in the FDT tension measurements was the difference between the graft tension measured by the FDT and the load cells. Results of the statistical analyses showed that neither the means of applying the calibration load, the number of flexion angles used for calibration, nor the tunnel size had a significant effect on the accuracy of the FDT. Thus a cable may be used instead of the graft to transmit loads to the FDT during calibration, thus simplifying the procedure. Accurate calibration requires data from just three flexion angles of 0, 45, and 90 deg and a curve fit to obtain a calibration curve over a continuous range of flexion within the limits of this angle group. Since friction did not adversely affect the measurement accuracy of the FDT, the femoral tunnel can be drilled to match the diameter of the graft and does not need to be overdrilled. Following these procedures, the error in measuring graft tension with the FDT averages less than 10 percent relative to a full-scale load of 257 N. 相似文献
49.
We propose a mathematical model for pendelluft flow in a single airway bifurcation. The model is motivated by an apparatus used in an experimental study of the pendelluft by Ultman et al. (1988). We derive differential equations governing the fluid flow, which directly connect physiological parameters to the variables determining the pendelluft; this approach allows us to include nonlinearity in the model. If nonlinearity is neglected, our model is identical to the R-I-C circuits used by previous investigators. If nonlinearity is retained, we show that pendelluft can occur even in perfectly symmetric airway bifurcations. For the specific apparatus used in the experiments of High et al. (1991), we demonstrate that two qualitatively different pendelluft flows can occur in the system. 相似文献
50.