全文获取类型
收费全文 | 1527篇 |
免费 | 144篇 |
国内免费 | 68篇 |
出版年
2023年 | 11篇 |
2022年 | 29篇 |
2021年 | 49篇 |
2020年 | 23篇 |
2019年 | 40篇 |
2018年 | 36篇 |
2017年 | 41篇 |
2016年 | 56篇 |
2015年 | 66篇 |
2014年 | 79篇 |
2013年 | 77篇 |
2012年 | 106篇 |
2011年 | 98篇 |
2010年 | 74篇 |
2009年 | 62篇 |
2008年 | 74篇 |
2007年 | 85篇 |
2006年 | 82篇 |
2005年 | 60篇 |
2004年 | 48篇 |
2003年 | 52篇 |
2002年 | 54篇 |
2001年 | 24篇 |
2000年 | 28篇 |
1999年 | 29篇 |
1998年 | 13篇 |
1997年 | 16篇 |
1996年 | 12篇 |
1995年 | 10篇 |
1994年 | 13篇 |
1993年 | 11篇 |
1992年 | 23篇 |
1991年 | 22篇 |
1990年 | 22篇 |
1989年 | 28篇 |
1988年 | 28篇 |
1987年 | 16篇 |
1986年 | 15篇 |
1985年 | 12篇 |
1984年 | 17篇 |
1983年 | 11篇 |
1982年 | 10篇 |
1981年 | 9篇 |
1980年 | 7篇 |
1979年 | 10篇 |
1978年 | 7篇 |
1977年 | 6篇 |
1976年 | 7篇 |
1973年 | 7篇 |
1972年 | 4篇 |
排序方式: 共有1739条查询结果,搜索用时 390 毫秒
971.
Jingjing Li Yujing Xia Tong Liu Junshan Wang Weiqi Dai Fan Wang Yuanyuan Zheng Kan Chen Sainan Li Abudumijiti Huerxidan Zheng Zhou Jianrong Wang Wenxia Lu Rong Zhu Jing Yang Huawei Zhang Qin Yin Chengfen Wang Yuqing Zhou Jie Lu Yingqun Zhou Chuanyong Guo 《PloS one》2015,10(3)
Objective
Astaxanthin, a potent antioxidant, exhibits a wide range of biological activities, including antioxidant, atherosclerosis and antitumor activities. However, its effect on concanavalin A (ConA)-induced autoimmune hepatitis remains unclear. The aim of this study was to investigate the protective effects of astaxanthin on ConA-induced hepatitis in mice, and to elucidate the mechanisms of regulation.Materials and Methods
Autoimmune hepatitis was induced in in Balb/C mice using ConA (25 mg/kg), and astaxanthin was orally administered daily at two doses (20 mg/kg and 40 mg/kg) for 14 days before ConA injection. Levels of serum liver enzymes and the histopathology of inflammatory cytokines and other maker proteins were determined at three time points (2, 8 and 24 h). Primary hepatocytes were pretreated with astaxanthin (80 μM) in vitro 24 h before stimulation with TNF-α (10 ng/ml). The apoptosis rate and related protein expression were determined 24 h after the administration of TNF-α.Results
Astaxanthin attenuated serum liver enzymes and pathological damage by reducing the release of inflammatory factors. It performed anti-apoptotic effects via the descending phosphorylation of Bcl-2 through the down-regulation of the JNK/p-JNK pathway.Conclusion
This research firstly expounded that astaxanthin reduced immune liver injury in ConA-induced autoimmune hepatitis. The mode of action appears to be downregulation of JNK/p-JNK-mediated apoptosis and autophagy. 相似文献972.
Caveolae and non-caveolar lipid rafts are two types of membrane lipid microdomains that play important roles in insulin-stimulated glucose uptake in adipocytes. In order to ascertain their specific functions in this process, caveolae were ablated by caveolin-1 RNA interference. In Cav-1 RNAi adipocytes, neither insulin-stimulated glucose uptake nor Glut-4 (glucose transporter 4) translocation to membrane lipid microdomains was affected by the ablation of caveolae. With a modified sucrose density gradient, caveolae and non-caveolar lipid rafts could be separated. In the wild-type 3T3- L l adipocytes, Glut-4 was found to be translocated into both caveolae and non-caveolar lipid rafts. However, in Cav1 RNAi adipocytes, Glut-4 was localized predominantly in non-caveolar lipid rafts. After the removal of insulin, caveolaelocalized Glut-4 was internalized faster than non-caveolar lipid raft-associated Glut-4. The internalization of Glut-4 from plasma membrane was significantly decreased in Cav-1 RNAi adipocytes. These results suggest that insulin-stimulated Glut-4 translocation and glucose uptake are caveolae-independent events. Caveolae play a role in the internalization of Glut-4 from plasma membrane after the removal of insulin. 相似文献
973.
Expression of the human fast-twitch skeletal muscle troponin I cDNA in a human ovarian carcinoma suppresses tumor growth 下载免费PDF全文
Xiong GuangWu Yang Li Wei YuQuan Wang ShiLang Tian Ling Lei Song Kan Bing Mao YongQiu 《中国科学C辑(英文版)》2007,50(1):93-100
To explore the efficiency and mechanism of ovarian carcinoma gene therapy with the human fast-twitch skeletal muscle troponin
I gene (Tnl-fast), Tnl-fast cDNA was transferred into human ovarian adenocarcinoma cell-line SK-OV-3. In vitro, the cell growth and cell cycle of Tnl-fast-, vector-, and mock-transfected cells were determined by MTT and flow cytometry
assay, respectively. The conditioned media of Tnl-fast-, vector-, and mock-transfected SK-OV-3 cells were collected, and the
cell proliferation inhibiting rates of human umbilical cord venous endothelial cells (HUVECs) by the three conditioned media
were assayed. All the three cell lines were implanted into node mice, and the tumor growth, cell apoptosis, angiogenesis,
and expression of Tnl-fast were observed or analyzed, respectively. In vitro, expression of Tnl-fast protein had no inhibiting effect on the growth of the dominant and stable transfectant cells, but
endothelium, when compared with vector-transfected cells and nontransfected parental SK-OV-3 cells. Implantation of stable
clone expressing Tnl-fast in the female BALB/c nude mice inhibits primary tumor growth by an average of 73%. The nude mice
grafts expressing Tnl-fast exhibit a significant decrease of microvascular density, a higher rate of tumor cells apoptosis
and a comparable proliferation rate as control. Our study, to our knowledge, shows the slowed down growth of the primary ovarian
carcinoma, suggested that grafts were self-inhibitory by halting angiogenesis. Our data might also provide a novel useful
strategy for cancer therapy by antiangiogenic gene therapy with a specific angiogenesis inhibitor Tnl-fast. 相似文献
974.
Champagne CE Goliber TE Wojciechowski MF Mei RW Townsley BT Wang K Paz MM Geeta R Sinha NR 《The Plant cell》2007,19(11):3369-3378
Across vascular plants, Class 1 KNOTTED1-like (KNOX1) genes appear to play a critical role in the development of compound leaves. An exception to this trend is found in the Fabaceae, where pea (Pisum sativum) uses UNIFOLIATA, an ortholog of the floral regulators FLORICAULA (FLO) and LEAFY (LFY), in place of KNOX1 genes to regulate compound leaf development. To assess the phylogenetic distribution of KNOX1-independent compound leaf development, a survey of KNOX1 protein expression across the Fabaceae was undertaken. The majority of compound-leafed Fabaceae have expression of KNOX1 proteins associated with developing compound leaves. However, in a large subclade of the Fabaceae, the inverted repeat-lacking clade (IRLC), of which pea is a member, KNOX1 expression is not associated with compound leaves. These data suggest that the FLO/LFY gene may function in place of KNOX1 genes in generating compound leaves throughout the IRLC. The contribution of FLO/LFY to leaf complexity in a member of the Fabaceae outside of the IRLC was examined by reducing expression of FLO/LFY orthologs in transgenic soybean (Glycine max). Transgenic plants with reduced FLO/LFY expression showed only slight reductions in leaflet number. Overexpression of a KNOX1 gene in alfalfa (Medicago sativa), a member of the IRLC, resulted in an increase in leaflet number. This implies that KNOX1 targets, which promote compound leaf development, are present in alfalfa and are still sensitive to KNOX1 regulation. These data suggest that KNOX1 genes and the FLO/LFY gene may have played partially overlapping roles in compound leaf development in ancestral Fabaceae but that the FLO/LFY gene took over this role in the IRLC. 相似文献
975.
Specialized roles of the two mitotic cyclins in somatic cells: cyclin A as an activator of M phase-promoting factor 下载免费PDF全文
The role of cyclin B-CDC2 as M phase-promoting factor (MPF) is well established, but the precise functions of cyclin A remain a crucial outstanding issue. Here we show that down-regulation of cyclin A induces a G2 phase arrest through a checkpoint-independent inactivation of cyclin B-CDC2 by inhibitory phosphorylation. The phenotype is rescued by expressing cyclin A resistant to the RNA interference. In contrast, down-regulation of cyclin B disrupts mitosis without inactivating cyclin A-CDK, indicating that cyclin A-CDK acts upstream of cyclin B-CDC2. Even when ectopically expressed, cyclin A cannot replace cyclin B in driving mitosis, indicating the specific role of cyclin B as a component of MPF. Deregulation of WEE1, but not the PLK1-CDC25 axis, can override the arrest caused by cyclin A knockdown, suggesting that cyclin A-CDK may tip the balance of the cyclin B-CDC2 bistable system by initiating the inactivation of WEE1. These observations show that cyclin A cannot form MPF independent of cyclin B and underscore a critical role of cyclin A as a trigger for MPF activation. 相似文献
976.
Qiao JX Wang TC Wang GZ Cheney DL He K Rendina AR Xin B Luettgen JM Knabb RM Wexler RR Lam PY 《Bioorganic & medicinal chemistry letters》2007,17(18):5041-5048
We previously reported a series of enantiopure cis-(1R,2S)-cyclopentyldiamine derivatives as potent and selective inhibitors of Factor Xa (FXa). Herein, we describe our approach to improve the metabolic stability of this series via core modifications. Multiple resulting series of compounds demonstrated similarly high FXa potency and improved metabolic stability in human liver microsomes compared with the cyclopentyldiamide 1. (3R,4S)-Pyrrolidinyldiamide 31 was the best overall compound with human FXa K(i) of 0.50 nM, PT EC(2x) of 2.1 microM in human plasma, bioavailability of 25% and t(1/2)of 2.7h in dogs. Further biochemical characterization of compound 31 is also presented. 相似文献
977.
Islam MK Tsuboya C Kusaka H Aizawa S Ueki T Michibata H Kanamori K 《Biochimica et biophysica acta》2007,1770(8):1212-1218
To better understand the mechanism of vanadium reduction in ascidians, we examined the reduction of vanadium(V) to vanadium(IV) by NADPH and the reduction of vanadium(IV) to vanadium(III) by L-cysteine methyl ester (CysME). UV-vis and electron paramagnetic resonance spectroscopic studies indicated that in the presence of several biologically relevant ligands vanadium(V) and vanadium(IV) were reduced by NADPH and CysME, respectively. Specifically, NADPH directly reduced vanadium(V) to vanadium(IV) with the assistance of ligands that have a formation constant with vanadium(IV) of greater than 7. Also, glycylhistidine and glycylaspartic acid were found to assist the reduction of vanadium(IV) to vanadium(III) by CysME. 相似文献
978.
The lipid-binding SEC14 domain 总被引:1,自引:0,他引:1
Protein-lipid interactions are important for protein targeting, signal transduction, lipid transport, lipid biosynthesis, lipid metabolism, and the maintenance of cellular compartments and membranes. Specific lipid-binding protein domains, such as PH, FYVE, PX, PHD, C2 and SEC14 homology domains, mediate interactions between proteins and specific phospholipids. Here we review the published literature, plus some of our most recent unpublished findings, regarding the biology of the SEC14 domain, also known as CRAL_TRIO domain. 相似文献
979.
The structural characteristics of Fusarium have received attention from both pure and applied scientists. Because many genes and physiological mechanisms are involved
in the development of a particular structure type, this research is complicated. For revealing the structure of macromolecule
in these fungal cells, FT-IR spectroscopy combined with multivariate statistical analysis was performed to characterize the
structure of protein and polysaccharide of spores and mycelia obtained from different culture medium. The second derivative
FT-IR spectra exhibited strain-specific infrared characteristics in the protein secondary structure sensitive amide I region.
The region between 750 and 950 cm−1 assigned to α-and β-glucans was investigated for studied samples. Principal components analysis (PCA) allowed us to separate
mycelia into two clusters according to different growth medium, indicating that spectra of strains may have been greatly affected
by cultivation conditions.
Published in Russian in Biokhimiya, 2007, Vol. 72, No. 1, pp. 72–79. 相似文献
980.