全文获取类型
收费全文 | 2911篇 |
免费 | 117篇 |
国内免费 | 223篇 |
出版年
2023年 | 11篇 |
2022年 | 39篇 |
2021年 | 52篇 |
2020年 | 51篇 |
2019年 | 76篇 |
2018年 | 60篇 |
2017年 | 45篇 |
2016年 | 45篇 |
2015年 | 104篇 |
2014年 | 191篇 |
2013年 | 180篇 |
2012年 | 168篇 |
2011年 | 243篇 |
2010年 | 175篇 |
2009年 | 113篇 |
2008年 | 158篇 |
2007年 | 164篇 |
2006年 | 132篇 |
2005年 | 116篇 |
2004年 | 96篇 |
2003年 | 98篇 |
2002年 | 76篇 |
2001年 | 60篇 |
2000年 | 58篇 |
1999年 | 49篇 |
1998年 | 51篇 |
1997年 | 61篇 |
1996年 | 61篇 |
1995年 | 46篇 |
1994年 | 76篇 |
1993年 | 46篇 |
1992年 | 52篇 |
1991年 | 49篇 |
1990年 | 37篇 |
1989年 | 42篇 |
1988年 | 21篇 |
1987年 | 21篇 |
1986年 | 25篇 |
1985年 | 22篇 |
1984年 | 14篇 |
1983年 | 8篇 |
1982年 | 9篇 |
1981年 | 5篇 |
1980年 | 7篇 |
1979年 | 8篇 |
1977年 | 6篇 |
1976年 | 4篇 |
1974年 | 3篇 |
1973年 | 4篇 |
1970年 | 3篇 |
排序方式: 共有3251条查询结果,搜索用时 15 毫秒
1.
《Cytokine》2015,74(2):245-252
BackgroundWe aimed to investigate the use of novel serum biomarkers for predicting the recurrence and survival of patients with hepatitis B virus (HBV)-related early hepatocellular carcinoma (HCC) after hepatic resection or radiofrequency ablation (RFA).MethodsOne hundred and five patients with HBV-related HCC, who fulfilled the Milan criteria without vascular invasion and underwent hepatic resection or RFA, were followed-up for a median duration of 52 months. Pretreatment serum concentrations of 16 cytokines including interleukin-6 (IL-6) were measured by using a Luminex 200 system. The measured serum cytokines and several clinical factors were analyzed retrospectively.ResultsUnivariate analysis showed that patients with lower pretreatment serum levels of IL-10, IL-6, monocyte chemoattractant protein-1, and tumor necrosis factor-α had significantly shorter disease-free survival (DFS) than those with higher levels. Multivariate analysis revealed that a low serum IL-6 level (⩽33.00 pg/mL; hazard ratio [HR] = 5.39; 95% confidence interval [CI] = 1.27–22.93; P = 0.022), low platelet count (<100 × 109/L; HR = 2.23; 95% CI = 1.28–3.89; P = 0.005), and low serum albumin level (⩽3.5 g/L; HR = 2.26; 95% CI = 1.28–3.97; P = 0.005) had a negative prognostic impact on DFS. In the analysis for overall survival, a low serum platelet level (<100 × 109/L; HR = 2.80; 95% CI = 1.31–5.99; P = 0.008) and multiple tumor (⩾2; HR = 4.05; 95% CI = 1.56–10.48; P = 0.004) showed a negative prognostic impact on the overall survival.ConclusionA low serum IL-6 level is, in addition to low platelet count and low serum albumin level, an independent prognostic factor for DFS in patients with HBV-related early HCC who underwent hepatic resection or RFA with curative intention. 相似文献
2.
Hepatitis C virus (HCV) core protein is known to induce promoter hypermethylation of tumor suppressor genes including E-cadherin to repress their expression when overexpressed in human hepatocytes; however, its actual role during HCV infection is still unknown. Here, we report that infection with HCV derived from pJFH-1 replicon system that mimics natural infection elevates protein levels of DNA methyltransferase 1 and 3b to enhance DNMT activity in human hepatocytes. As a consequence, HCV induced promoter hypermethylation of E-cadherin, resulting in repression of its expression. In addition down-regulation of E-cadherin by HCV led to epithelial–mesenchymal transition that is known to be a critical event during the late stage of tumorigenesis. 相似文献
3.
In non-polarized cell culture models, influenza virus has been shown to enter host cells via multiple endocytic pathways, including classical clathrin-mediated endocytic routes (CME), clathrin- and caveolae-independent routes and macropinocytosis. However, little is known about the entry route of influenza virus in differentiated epithelia, in vivo site of infection for influenza virus. Here, we show that in polarized Madin–Darby canine kidney type II (MDCK II) cells, influenza virus has a specific utilization of the clathrin-mediated endocytic pathway and requires Eps15 for host cell entry. 相似文献
4.
A. Benito E. Viaplana J.L. Corchero X. Carbonell A. Villaverde 《FEMS microbiology letters》1995,129(2-3):157-162
Abstract The 3D gene of foot-and-mouth disease virus encodes the viral RNA dependent RNA polymerase, also called virus infection associated (VIA) antigen, which is the most important serological marker of virus infection. This 3D gene from a serotype Cl virus has been cloned and overexpressed in Escherichia coli under the control of the strong lambda lytic promoters. The resulting 51 kDa recombinant protein has been shown to be immunoreactive with sera from infected animals. After induction of gene expression, an immediate and dramatic arrest of cell DNA synthesis occurs, similar to that produced by genotoxic doses of the drug mitomycin C. This effect does not occur during the production of either a truncated VIA antigen or other related and non-related viral proteins. The inhibition of DNA replication results in a subsequent induction of the host SOS DNA-repair response and in an increase of the mutation frequency in the surviving cells. 相似文献
5.
Zaki Monawar Eisa 《Saudi Journal of Biological Sciences》2011,18(2):195-200
Hepatitis C virus (HCV) causes serious infections in the liver which may lead to liver cirrhosis and hepatocellular carcinoma. Non structural 3 (NS3) protein is one of the most important proteins of the virus which has protease and helicase activities. Protease activity has a crucial role in the replication and persistence of the virus. Site directed mutation was carried out in the protease region of one NS3 and another site directed mutation in the helicase region of another NS3. The expression of both mutated NS3 was compared with wild NS3. Expression of the three different NS3 types was confirmed by in situ staining and western blotting using an anti-NS3 antibody and correlated with a reduced antiviral response after treatment with interferon-α. Mutation analysis showed that the NS3 protease activity andnot the NS3 helicase was essential for the inhibition of the interferon-α response. 相似文献
6.
Sandrine Belouzard Ikenna Madu Gary R. Whittaker 《The Journal of biological chemistry》2010,285(30):22758-22763
Proteolytic priming is a common method of controlling the activation of membrane fusion mediated by viral glycoproteins. The severe acute respiratory syndrome coronavirus spike protein (SARS-CoV S) can be primed by a variety of host cell proteases, with proteolytic cleavage occurring both as the S1/S2 boundary and adjacent to a fusion peptide in the S2 domain. Here, we studied the priming of SARS-CoV S by elastase and show an important role for residue Thr795 in the S2 domain. A series of alanine mutants were generated in the vicinity of the S2 cleavage site, with the goal of examining elastase-mediated cleavage within S2. Both proteolytic cleavage and fusion activation were modulated by altering the cleavage site position. We propose a novel mechanism whereby SARS-CoV fusion protein function can be controlled by spatial regulation of the proteolytic priming site, with important implications for viral pathogenesis. 相似文献
7.
Early Inhibition of Acetylcholinesterase and Choline Acetyltransferase Activity in Herpes simplex Virus Type 1 Infection of PC12 Cells 总被引:1,自引:0,他引:1
Abstract: Early in the course of productive Herpes simplex virus type 1 (HSV-1) infection of PC12 cells, activities of both acetylcholinesterase (AChE) and choline acetyltransferase (CAT) fell. Studies using metabolic inhibitors and a temperature-sensitive mutant of the virus suggested that the decline in activities of both enzymes was associated with events occurring early in the replicative cycle related to expression of the immediate-early (α) group of viral polypeptides. HSV-1 gene products thus may alter specialized cell functions well before the production of viral progeny and initiation of cell lysis. The early clinical manifestations of nervous system viral infection may reflect focal metabolic disturbance rather than, or in addition to, simple cell death. 相似文献
8.
S20Y murine neuroblastoma cells appear to express a protein component(s) able to adhere specifically to the oligosaccharide portion of GM1 (oligo-GM1). To identify proteins with which the oligo-GM1 becomes closely associated, a radiolabeled (125I), photoactivatable derivative of oligo-GM1 was prepared. This was accomplished by reductive amination of the glucosyl moiety of oligo-GM1 to 1-deoxy-1-aminoglucitol, followed by reaction of the amine with sulfosuccinimidyl 2-(p-azidosalicylamido)ethyl-1,3'-dithiopropionate (SASD). Crosslinking studies using the photoactivatable probe indicated that it came in close proximity to a protein with an apparent molecular mass of approximately 71 kDa. In competition experiments, as little as a 10-fold molar excess of oligo-GM1 resulted in a selective reduction in labeling of this protein; preincubation with a 200-fold molar excess of siayllactose was necessary to observe the same change in the labeling pattern, lending additional support to the hypothesis that the approximately 71-kDa protein specifically associates with oligo-GM1. Cell surface location of the oligo-GM1 binding protein was confirmed using subcellular fractionation and morphological analyses. 相似文献
9.
300例慢乙肝病情轻重的相关危险因素临床分析 总被引:1,自引:0,他引:1
目的探讨慢乙肝病情轻重程度与相关临床因素的相关性。方法选择300例慢乙肝患者,按照标准分为慢乙肝轻度、中度、重度,慢乙肝重型,肝炎肝硬化五个观察组,分析乙肝病毒DNA载量、中草药干预、饮酒、合并症用药,HBeAg+/HBeAg-及年龄等因素在不同观察组中的分布情况。结果以上相关因素在慢乙肝重度、肝硬化观察组的分布与轻、中度观察组相比有明显差异;相关因素并存越多,病情越重。结论乙肝病毒DNA载量、中草药干预、饮酒、合并症用药,HBeAg+/HBeAg-及年龄等与慢乙肝病情轻重之间存在一定的相关性。 相似文献
10.
S/D法灭活血液制剂中脂包膜病毒效果验证的研究 总被引:3,自引:2,他引:1
选用不同核酸的脂包膜病毒,其中RNA病毒为水疱性口炎病毒(VSV),DNA病毒为伪狂犬病毒(PRV),将两种指示病毒分别用于验证S/D法处理对纤维蛋白原、凝血酶原复合物、凝血因子Ⅷ、静注丙种球蛋白、免疫血浆等血液制剂的病毒灭活效果。结果该法对所有被处理的血液制剂中的PRV及VSV灭活能力分别为≥3.38~5.88和≥3.50~4.75logTCID50/0.1ml,表明S/D法对两种病毒核酸类型的脂包膜病毒有良好的灭活效果。 相似文献