全文获取类型
收费全文 | 6265篇 |
免费 | 442篇 |
国内免费 | 2篇 |
专业分类
6709篇 |
出版年
2023年 | 23篇 |
2022年 | 82篇 |
2021年 | 158篇 |
2020年 | 73篇 |
2019年 | 98篇 |
2018年 | 137篇 |
2017年 | 121篇 |
2016年 | 201篇 |
2015年 | 290篇 |
2014年 | 326篇 |
2013年 | 420篇 |
2012年 | 529篇 |
2011年 | 603篇 |
2010年 | 318篇 |
2009年 | 280篇 |
2008年 | 371篇 |
2007年 | 435篇 |
2006年 | 365篇 |
2005年 | 328篇 |
2004年 | 305篇 |
2003年 | 315篇 |
2002年 | 302篇 |
2001年 | 54篇 |
2000年 | 28篇 |
1999年 | 42篇 |
1998年 | 47篇 |
1997年 | 43篇 |
1996年 | 32篇 |
1995年 | 31篇 |
1994年 | 18篇 |
1993年 | 21篇 |
1992年 | 15篇 |
1991年 | 14篇 |
1989年 | 12篇 |
1988年 | 9篇 |
1987年 | 8篇 |
1985年 | 8篇 |
1984年 | 11篇 |
1982年 | 11篇 |
1981年 | 10篇 |
1980年 | 12篇 |
1977年 | 21篇 |
1976年 | 18篇 |
1975年 | 12篇 |
1973年 | 9篇 |
1972年 | 12篇 |
1969年 | 10篇 |
1968年 | 13篇 |
1967年 | 7篇 |
1966年 | 11篇 |
排序方式: 共有6709条查询结果,搜索用时 15 毫秒
71.
BJ Ku TH Kim JH Lee ED Buras LD White RD Stevens OR Ilkayeva JR Bain CB Newgard FJ Demayo JW Jeong 《PloS one》2012,7(8):e42915
The disruption of cholesterol homeostasis leads to an increase in cholesterol levels which results in the development of cardiovascular disease. Mitogen Inducible Gene 6 (Mig-6) is an immediate early response gene that can be induced by various mitogens, stresses, and hormones. To identify the metabolic role of Mig-6 in the liver, we conditionally ablated Mig-6 in the liver using the Albumin-Cre mouse model (Alb(cre/+)Mig-6(f/f); Mig-6(d/d)). Mig-6(d/d) mice exhibit hepatomegaly and fatty liver. Serum levels of total, LDL, and HDL cholesterol and hepatic lipid were significantly increased in the Mig-6(d/d) mice. The daily excretion of fecal bile acids was significantly decreased in the Mig-6(d/d) mice. DNA microarray analysis of mRNA isolated from the livers of these mice showed alterations in genes that regulate lipid metabolism, bile acid, and cholesterol synthesis, while the expression of genes that regulate biliary excretion of bile acid and triglyceride synthesis showed no difference in the Mig-6(d/d) mice compared to Mig-6(f/f) controls. These results indicate that Mig-6 plays an important role in cholesterol homeostasis and bile acid synthesis. Mice with liver specific conditional ablation of Mig-6 develop hepatomegaly and increased intrahepatic lipid and provide a novel model system to investigate the genetic and molecular events involved in the regulation of cholesterol homeostasis and bile acid synthesis. Defining the molecular mechanisms by which Mig-6 regulates cholesterol homeostasis will provide new insights into the development of more effective ways for the treatment and prevention of cardiovascular disease. 相似文献
72.
Regalado EL Rodríguez M Menéndez R Concepción AA Nogueiras C Laguna A Rodríguez AA Williams DE Lorenzo-Luaces P Valdés O Hernandez Y 《Marine biotechnology (New York, N.Y.)》2009,11(1):74-80
Daily topical application of the aqueous ethanolic extract of the marine sea grass, Thalassia testudinum, on mice skin exposed to UVB radiation resulted in a dose-dependent recovery of the skin macroscopic alterations over a 6-day
period. Maximal effect (90%) occurred at a dose of 240 μg/cm2, with no additional effects at higher doses. Bioassay-guided fractionation of the plant extract resulted in the isolation
of thalassiolin B (1). Topical application of 1 (240 μg/cm2) markedly reduces skin UVB-induced damage. In addition, thalassiolin B scavenged 2,2-diphenyl-2-picrylhydrazyl radical with
an EC50 = 100 μg/ml. These results suggest that thalassiolin B is responsible for the skin-regenerating effects of the crude extract
of T. testudinum.
Erik L. Regalado and María Rodríguez have contributed equally to this work and should be considered as first authors. 相似文献
73.
Agromayor M Soler N Caballe A Kueck T Freund SM Allen MD Bycroft M Perisic O Ye Y McDonald B Scheel H Hofmann K Neil SJ Martin-Serrano J Williams RL 《Structure (London, England : 1993)》2012,20(3):414-428
- Download : Download high-res image (337KB)
- Download : Download full-size image
74.
Gabbasov ZA Kozlov SG Imaeva AE Saburova OS Zykov KA Masenko VP Smirnov VN 《Canadian journal of physiology and pharmacology》2011,89(6):413-418
The aim of this study was to assess the involvement of eosinophil cationic protein, a marker of eosinophil activation, in the development of in-stent restenosis after drug-eluting stent implantation. Follow-up angiography at 6 to 12?months was performed in 32 patients who were treated with percutaneous coronary intervention and implantation of sirolimus-eluting stents. Blood plasma levels of eosinophil cationic protein (ECP) and total immunoglobulin E (IgE) were measured by enzyme-linked immunosorbent assay and the level of C-reactive protein (hs-CRP) by high-sensitivity nephelometry. According to angiography data, in-stent restenosis occurred in 13 patients, while 19 patients did not develop it. There were no differences between the hs-CRP and IgE levels in patients with or without restenosis. In contrast, ECP level was higher in patients with restenosis compared with that in patients without restenosis [17.7?ng/mL (11.2-24.0) vs. 9.0?ng/mL (6.4-12.9), p?= 0.017]. The incidence of in-stent restenoses was 63% in patients with ECP level higher than or equal to 11?ng/mL, and 19% in patients with an ECP level lower than 11?ng/mL (p?= 0.019). These findings suggest that elevated eosinophil activation may play an important role in the pathogenesis of in-stent restenosis after implantation of drug-eluting stents. 相似文献
75.
76.
Chinthamani S Odusanwo O Mondal N Nelson J Neelamegham S Baker OJ 《American journal of physiology. Cell physiology》2012,302(7):C968-C978
Lipoxins are formed by leukocytes during cell-cell interactions with epithelial or endothelial cells. Native lipoxin A(4) (LXA(4)) binds to the G protein-coupled lipoxin receptors formyl peptide receptor 2 (FPR2)/ALX and CysLT1. Furthermore, LXA(4) inhibits recruitment of neutrophils, by attenuating chemotaxis, adhesion, and transmigration across vascular endothelial cells. LXA(4) thus appears to serve as an endogenous "stop signal" for immune cell-mediated tissue injury (Serhan CN; Annu Rev Immunol 25: 101-137, 2007). The role of LXA(4) has not been addressed in salivary epithelium, and little is known about its effects on vascular endothelium. Here, we determined that interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) receptor activation in vascular endothelium and salivary epithelium upregulated the expression of adhesion molecules that facilitates the binding of immune cells. We hypothesize that the activation of the ALX/FPR2 and/or CysLT1 receptors by LXA(4) decreases this cytokine-mediated upregulation of cell adhesion molecules that enhance lymphocyte binding to both the vascular endothelium and salivary epithelium. In agreement with this hypothesis, we observed that nanomolar concentrations of LXA(4) blocked IL-1β- and TNF-α-mediated upregulation of E-selectin and intercellular cell adhesion molecule-1 (ICAM-1) on human umbilical vein endothelial cells (HUVECs). Binding of Jurkat cells to stimulated HUVECs was abrogated by LXA(4). Furthermore, LXA(4) preincubation with human submandibular gland cell line (HSG) also blocked TNF-α-mediated upregulation of vascular cell adhesion molecule-1 (VCAM-1) in these cells, and it reduced lymphocyte adhesion. These findings suggest that ALX/FPR2 and/or CysLT1 receptor activation in endothelial and epithelial cells blocks cytokine-induced adhesion molecule expression and consequent binding of lymphocytes, a critical event in the pathogenesis of Sj?gren's syndrome (SS). 相似文献
77.
78.
Identification of determinants involved in initiation of hepatitis C virus RNA synthesis by using intergenotypic replicase chimeras
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)
Binder M Quinkert D Bochkarova O Klein R Kezmic N Bartenschlager R Lohmann V 《Journal of virology》2007,81(10):5270-5283
The 5' nontranslated region (NTR) and the X tail in the 3' NTR are the least variable parts of the hepatitis C virus (HCV) genome and play an important role in the initiation of RNA synthesis. By using subgenomic replicons of the HCV isolates Con1 (genotype 1) and JFH1 (genotype 2), we characterized the genotype specificities of the replication signals contained in the NTRs. The replacement of the JFH1 5' NTR and X tail with the corresponding Con1 sequence resulted in a significant decrease in replication efficiency. Exchange of the X tail specifically reduced negative-strand synthesis, whereas substitution of the 5' NTR impaired the generation of progeny positive strands. In search for the proteins involved in the recognition of genotype-specific initiation signals, we analyzed recombinant nonstructural protein 5B (NS5B) RNA polymerases of both isolates and found some genotype-specific template preference for the 3' end of positive-strand RNA in vitro. To further address genotype specificity, we constructed a series of intergenotypic replicon chimeras. When combining NS3 to NS5A of Con1 with NS5B of JFH1, we observed more-efficient replication with the genotype 2a X tail, indicating that NS5B recognizes genotype-specific signals in this region. In contrast, a combination of the NS3 helicase with NS5A and NS5B was required to confer genotype specificity to the 5' NTR. These results present the first genetic evidence for an interaction between helicase, NS5A, and NS5B required for the initiation of RNA synthesis and provide a system for the specific analysis of HCV positive- and negative-strand syntheses. 相似文献
79.
Gabriele Marcian Midori Ishii Olga O. Nerusheva Bungo Akiyoshi 《The Journal of cell biology》2021,220(8)
The kinetochore is the macromolecular protein complex that assembles onto centromeric DNA and binds spindle microtubules. Evolutionarily divergent kinetoplastids have an unconventional set of kinetochore proteins. It remains unknown how kinetochores assemble at centromeres in these organisms. Here, we characterize KKT2 and KKT3 in the kinetoplastid parasite Trypanosoma brucei. In addition to the N-terminal kinase domain and C-terminal divergent polo boxes, these proteins have a central domain of unknown function. We show that KKT2 and KKT3 are important for the localization of several kinetochore proteins and that their central domains are sufficient for centromere localization. Crystal structures of the KKT2 central domain from two divergent kinetoplastids reveal a unique zinc-binding domain (termed the CL domain for centromere localization), which promotes its kinetochore localization in T. brucei. Mutations in the equivalent domain in KKT3 abolish its kinetochore localization and function. Our work shows that the unique central domains play a critical role in mediating the centromere localization of KKT2 and KKT3. 相似文献
80.
Julio Álvarez Andrés Perez Sergio Marqués Javier Bezos Anna Grau Maria Luisa de la Cruz Beatriz Romero Jose Luis Saez Maria del Rosario Esquivel Maria del Carmen Martínez Olga Mínguez Lucía de Juan Lucas Domínguez 《BMC veterinary research》2014,10(1):1-10