全文获取类型
收费全文 | 3050篇 |
免费 | 152篇 |
国内免费 | 1篇 |
出版年
2024年 | 4篇 |
2023年 | 16篇 |
2022年 | 45篇 |
2021年 | 67篇 |
2020年 | 45篇 |
2019年 | 58篇 |
2018年 | 71篇 |
2017年 | 70篇 |
2016年 | 125篇 |
2015年 | 170篇 |
2014年 | 221篇 |
2013年 | 217篇 |
2012年 | 262篇 |
2011年 | 241篇 |
2010年 | 168篇 |
2009年 | 138篇 |
2008年 | 187篇 |
2007年 | 171篇 |
2006年 | 127篇 |
2005年 | 120篇 |
2004年 | 126篇 |
2003年 | 90篇 |
2002年 | 83篇 |
2001年 | 74篇 |
2000年 | 68篇 |
1999年 | 43篇 |
1998年 | 16篇 |
1997年 | 14篇 |
1996年 | 14篇 |
1995年 | 7篇 |
1994年 | 4篇 |
1993年 | 5篇 |
1992年 | 15篇 |
1991年 | 12篇 |
1990年 | 11篇 |
1989年 | 14篇 |
1988年 | 9篇 |
1987年 | 6篇 |
1986年 | 6篇 |
1985年 | 9篇 |
1984年 | 5篇 |
1983年 | 4篇 |
1982年 | 6篇 |
1979年 | 9篇 |
1978年 | 4篇 |
1975年 | 4篇 |
1974年 | 5篇 |
1973年 | 4篇 |
1972年 | 3篇 |
1968年 | 2篇 |
排序方式: 共有3203条查询结果,搜索用时 765 毫秒
241.
Soo-A Jung Yong-Man Park Seung-Woo Hong Jai-Hee Moon Jae-Sik Shin Ha-Reum Lee Seung-Hee Ha Dae-Hee Lee Jeong Hee Kim Seung-Mi Kim Jeong Eun Kim Kyu-pyo Kim Yong Sang Hong Eun Kyung Choi Jung Shin Lee Dong-Hoon Jin TaeWon Kim 《The Journal of biological chemistry》2015,290(16):9974-9985
YM155, which blocks the expression of survivin, a member of the inhibitor of apoptosis (IAP) family, induces cell death in a variety of cancer types, including prostate, bladder, breast, leukemia, and non-small lung cancer. However, the mechanism underlying gastric cancer susceptibility and resistance to YM155 is yet to be specified. Here, we demonstrate that cIAP1 stability dictates resistance to YM155 in human gastric cancer cells. Treatment of human gastric cancer cells with YM155 differentially induced cell death dependent on the stability of cIAP1 as well as survivin. Transfection with cIAP1 expression plasmids decreased cell sensitivity to YM155, whereas knockdown of endogenous cIAP1 using RNA interference enhanced sensitivity to YM155. In addition, double knockdown of survivin and cIAP1 significantly induced cell death in the YM155-resistant cell line, MKN45. We also showed that YM155 induced autoubiquitination and proteasome-dependent degradation of cIAP1. Surprisingly, survivin affected the stability of cIAP1 through binding, contributing to cell sensitivity to YM155. Thus, our findings reveal that YM155 sensitizes human gastric cancer cells to apoptotic cell death by degrading cIAP1, and furthermore, cIAP1 in gastric cancer cells may act as a PD marker for YM155 treatment. 相似文献
242.
Saussurea lappa has been reported to possess anti-atopic properties. In this study, we have confirmed the S. lappa’s anti-atopic properties in Nc/Nga mice and investigated the candidate gene related with its properties using microarray. We determined the target gene using real time PCR in in vitro experiment. S. lappa showed the significant reduction in atoptic dermatitis (AD) score and immunoglobulin E compared with the AD induced Nc/Nga mice. In the results of microarray using back skin obtained from animals, we found that S. lappa’s properties are closely associated with cytokine-cytokine receptor interaction and the JAK-STAT signaling pathway. Consistent with the microarray data, real-time RT-PCR confirmed these modulation at the mRNA level in skin tissues from S. lappa-treated mice. Among these genes, PI3Kca and IL20Rβ were significantly downregulated by S. lappa treatment in Nc/Nga mouse model. In in vitro experiment using HaCaT cells, we found that the S. lappa components, including alantolactone, caryophyllene, costic acid, costunolide and dehydrocostus lactone significantly decreased the expression of PI3Kca but not IL20Rβ in vitro. Therefore, our study suggests that PI3Kca-related signaling is closely related with the protective effects of S. lappa against the development of atopic-dermatitis. 相似文献
243.
244.
245.
246.
Kim BC Zhao X Ahn HK Kim JH Lee HJ Kim KW Nair S Hsiao E Jia H Oh MK Sang BI Kim BS Kim SH Kwon Y Ha S Gu MB Wang P Kim J 《Biosensors & bioelectronics》2011,26(5):1980-1986
This paper describes highly stable enzyme precipitate coatings (EPCs) on electrospun polymer nanofibers and carbon nanotubes (CNTs), and their potential applications in the development of highly sensitive biosensors and high-powered biofuel cells. EPCs of glucose oxidase (GOx) were prepared by precipitating GOx molecules in the presence of ammonium sulfate, then cross-linking the precipitated GOx aggregates on covalently attached enzyme molecules on the surface of nanomaterials. EPCs-GOx not only improved enzyme loading, but also retained high enzyme stability. For example, EPC-GOx on CNTs showed a 50 times higher activity per unit weight of CNTs than the conventional approach of covalent attachment, and its initial activity was maintained with negligible loss for 200 days. EPC-GOx on CNTs was entrapped by Nafion to prepare enzyme electrodes for glucose sensors and biofuel cells. The EPC-GOx electrode showed a higher sensitivity and a lower detection limit than an electrode prepared with covalently attached GOx (CA-GOx). The CA-GOx electrode showed an 80% drop in sensitivity after thermal treatment at 50°C for 4 h, while the EPC-GOx electrode maintained its high sensitivity with negligible decrease under the same conditions. The use of EPC-GOx as the anode of a biofuel cell improved the power density, which was also stable even after thermal treatment of the enzyme anode at 50°C. The excellent stability of the EPC-GOx electrode together with its high current output create new potential for the practical applications of enzyme-based glucose sensors and biofuel cells. 相似文献
247.
248.
Microwave-accelerated energy-efficient esterification of free fatty acid with a heterogeneous catalyst 总被引:1,自引:0,他引:1
Kim D Choi J Kim GJ Seol SK Ha YC Vijayan M Jung S Kim BH Lee GD Park SS 《Bioresource technology》2011,102(3):3639-3641
This paper shows energy-efficiency of microwave-accelerated esterification of free fatty acid with a heterogeneous catalyst by net microwave power measurement. In the reaction condition of 5 wt% sulfated zirconia and 1:20 M ratio of oil to methanol at 60°C and atmospheric pressure, more than 90% conversion of the esterification was achieved in 20 min by microwave heating, while it took about 130 min by conventional heating. Electric energy consumption for the microwave heating in this accelerated esterification was only 67% of estimated minimum heat energy demand because of significantly reduced reaction time. 相似文献
249.
Ghoneim OM Ibrahim DA El-Deeb IM Lee SH Booth RG 《Bioorganic & medicinal chemistry letters》2011,21(22):6714-6723
Autism symptoms are currently modulated by Selective Serotonin Reuptake Inhibitors (SSRIs). SSRIs slow onset of action limits their efficiency. The established synergistic activity of SSRIs and 5HT(1B/1D) autoreceptors antagonists motivated us to incorporate SSRIs and 5HT(1B/1D) antagonists in one 'hybrid' molecule. A library of virtual 'hybrid' molecules was designed using the tethering technique. A pharmacophore model was generated derived from 16 structurally diverse SSRIs (K(i)=0.013-5000 nM) and used as 3D query. Compounds with fit values (≥2) were chosen for synthesis and subsequent in vitro biological evaluation. Our pharmacophore model is a promising milestone to a class of SSRIs with dual action. 相似文献
250.
Heterocyclic analogs of ceramide as 3-alkanoyl or benzoyl-4-(1-hydroxy-2-enyl)-oxazolidin-2-ones were designed by binding of primary alcohol and amide in sphinogosine backbone as a carbamate. They were synthesized by addition of acyl halide to the common ring 4-(1-t-butyldimethylsilyloxyhexadec-2-enyl)-oxazolidin-2-one which was elaborated from chiral aziridine-2-carboxylate including stereoselective reduction and ring opening reactions as key steps. Other analogs with different carbon frame at C4 position which is corresponding to the sphingoid backbone were prepared from 3-cyclopentanecarbonyl-4-(1-t-butyldimethylsilyloxybut-2-enyl)-oxazolidin-2-one and straight and cyclic alkenes by cross metathesis. All compounds were tested as antileukemic drugs against human leukemia HL-60 cells. Many of them including propionyl, cyclopentanoyl and p-nitrobenzoyl-4-(1-hydroxyhexadec-2-enyl)-oxazolidin-2-ones showed better antileukemic activities than natural C2-ceramide with good correlation between cell death and DNA fragmentation. There is a drastic change of the activities by the carbon chain lengths at C4 position. Cytotoxicity was induced by caspase activation without significant accumulation of endogenous ceramide concentration or any perturbation of ceramide metabolism. 相似文献