全文获取类型
收费全文 | 1103篇 |
免费 | 42篇 |
国内免费 | 26篇 |
专业分类
1171篇 |
出版年
2023年 | 9篇 |
2022年 | 7篇 |
2021年 | 13篇 |
2020年 | 6篇 |
2019年 | 21篇 |
2018年 | 12篇 |
2017年 | 9篇 |
2016年 | 11篇 |
2015年 | 55篇 |
2014年 | 143篇 |
2013年 | 162篇 |
2012年 | 162篇 |
2011年 | 109篇 |
2010年 | 72篇 |
2009年 | 24篇 |
2008年 | 27篇 |
2007年 | 32篇 |
2006年 | 23篇 |
2005年 | 30篇 |
2004年 | 18篇 |
2003年 | 23篇 |
2002年 | 27篇 |
2001年 | 13篇 |
2000年 | 11篇 |
1999年 | 15篇 |
1998年 | 9篇 |
1997年 | 16篇 |
1996年 | 10篇 |
1995年 | 13篇 |
1994年 | 9篇 |
1993年 | 11篇 |
1992年 | 7篇 |
1991年 | 12篇 |
1990年 | 5篇 |
1989年 | 2篇 |
1988年 | 5篇 |
1987年 | 2篇 |
1985年 | 2篇 |
1984年 | 2篇 |
1983年 | 2篇 |
1982年 | 3篇 |
1981年 | 3篇 |
1980年 | 4篇 |
1979年 | 5篇 |
1978年 | 2篇 |
1976年 | 2篇 |
1973年 | 1篇 |
1972年 | 3篇 |
1971年 | 5篇 |
1970年 | 2篇 |
排序方式: 共有1171条查询结果,搜索用时 15 毫秒
981.
Glutamate Uptake and Metabolism in C-6 Glioma Cells: Alterations by Potassium Ion and Dibutyryl cAMP
Abstract: Uptake and metabolism of glutamate was studied in the C-6 glioma cell line grown in the absence or presence of dibutyryl cyclic AMP (dbcAMP). Glutamate and aspartate uptake were competitive in cells grown under both conditions. Increased [K+] in the medium caused a significant decrease in the uptake of both amino acids. A small part of this decrease (<25%) was due to an enhanced efflux of tissue amino acid. The effects of increased [K+] were observed whether or not the [Na+] in the medium was concomitantly decreased. In cells grown in the presence of 1 mM dbcAMP for 48 h, glutamate uptake and metabolism were altered. Tissue levels of glutamate, aspartate, glutamine, GABA, and alanine were generally less in treated than in naive cells. When incubated with 50 μM [U-14C]glutamate, there was significantly less incorporation of radioactivity into treated cells with time, resulting in greatly lowered specific radioactivities of glutamate, aspartate, and GABA. However, the rate of labeling of glutamine was greatly increased; this was consistent with the previously observed doubling in glutamine synthetase activity in dbcAMP-treated C-6 cells. Tissue glutamate decarboxylase activity was halved in treated cells, accounting for the large decrease in GABA labeling. The metabolic data suggested a decreased uptake of exogenous glutamate; in studies on initial rates of uptake, the Vmax of high-affinity glutamate uptake was decreased by 40%. This decrease was of the same order of magnitude as that observed in the metabolic experiments. Thus, in this glial model, both rapid, acute changes and slower, long-term changes in neuroactive amino acid metabolism were observed. Each of these conditions mimics a stimulus of neuronal origin, and the resulting changes could modulate extrasynaptic activity of neuroactive amino acids. 相似文献
982.
Yoshiaki Takahashi Hironori Arakawa Hideki Sugihara Kohjiro Hara Ashraful Islam Ryuzi Katoh Yasuhiro Tachibana Masatoshi Yanagida 《Inorganica chimica acta》2000,310(2):169-174
A series of mono-cationic polypyridyl-ruthenium complexes with strongly electron donating β-diketonate ligands {(dcbp)2Ru(L)}Cl, where DCBP=4,4′-dicarboxy-2,2′-bipyridine; L=acetylacetonate (1), 3-methyl-2,4-pentanedionate (2), 1,3-diphenyl-1,3-propanedionate (3), have been synthesized as molecular photosensitizers for a nanocrystalline TiO2 electrode. In alkaline methanol solution, these complexes exhibit intense visible light absorption with low energy MLCT maxima above 517 nm which accompany a significantly enhanced band tail, improving red light absorptivity beyond 600 nm. The photoelectrochemical properties of these three diketonate complexes on a TiO2 semiconductor have been compared to cis-dithiocyanate complex, (dcbp)2Ru(NCS)2, which is one of the most efficient sensitizers reported to date. The diketonate complexes show quite high performances in photoelectrochemical cells containing I−/I3 − electrolyte. The overall solar light-to-electrical energy conversion efficiencies are in the range of 6.0–3.9% while the dithiocyanate complex yields 5.7% efficiency in our experiments. 相似文献
983.
Keshuo Ding Arindam Banerjee Sheng Tan JunSong Zhao Qian Zhuang Rui Li Pengxu Qian Suling Liu Zheng-Sheng Wu Peter E. Lobie Tao Zhu 《The Journal of biological chemistry》2014,289(23):16057-16071
Previous studies have demonstrated that Artemin (ARTN) functions as a cancer stem cell (CSC) and metastatic factor in mammary carcinoma. Herein, we report that ARTN mediates acquired resistance to trastuzumab in HER2-positive mammary carcinoma cells. Ligands that increase HER2 activity increased ARTN expression in HER2-positive mammary carcinoma cells, whereas trastuzumab inhibited ARTN expression. Forced expression of ARTN decreased the sensitivity of HER2-positive mammary carcinoma cells to trastuzumab both in vitro and in vivo. Conversely, siRNA-mediated depletion of ARTN enhanced trastuzumab efficacy. Cells with acquired resistance to trastuzumab exhibited increased ARTN expression, the depletion of which restored trastuzumab sensitivity. Trastuzumab resistance produced an increased CSC population concomitant with enhanced mammospheric growth. ARTN mediated the enhancement of the CSC population by increased BCL-2 expression, and the CSC population in trastuzumab-resistant cells was abrogated upon inhibition of BCL-2. Hence, we conclude that ARTN is one mediator of acquired resistance to trastuzumab in HER2-positive mammary carcinoma cells. 相似文献
984.
组织工程三大要素为种子细胞、支架材料和信号分子,干细胞因其多分化潜能成为热门的种子细胞。血管化问题是制约工程化组织应用于临床的问题之一。利用干细胞构建组织工程血管的手段之一是在分离培养得到足够的种子细胞后,通过生长因子、细胞外基质、外力作用、其他细胞等的调控实现内皮向分化。只有实现了成功的血管构建,工程化组织才能正常的发挥作用。近年来不少国内外专家学者通过细胞联合培养的方法,观察细胞间的相互作用对血管构建的影响,结果表明,细胞联合培养在血管的形成、存活、稳定方面起到了重要的作用,为组织工程血管化提供了有效的途径,本文就部分细胞联合培养在血管构建中的作用作一综述。 相似文献
985.
Karin A. Simon-Giavarotti Leandro Giavarotti Ligia F. Gomes Alessandra F. Lima Adriano M. Veridiano Eduardo A. Garcia 《Free radical research》2013,47(10):1033-1039
The role of Kupffer cells in the hepatocellular injury and oxidative stress induced by lindane (20 mg/kg; 24 h) in hyperthyroid rats (daily doses of 0.1 mg l -3,3',5-triiodothyronine (T 3 )/kg for three consecutive days) was assessed by the simultaneous administration of gadolinium chloride (GdCl 3 ; 2 doses of 10 mg/kg on alternate days). Hyperthyroid animals treated with lindane exhibit enhanced liver microsomal superoxide radical ( O2.-) production and NADPH cytochrome c reductase activity, with lower levels of cytochrome P450, superoxide dismutase (SOD) and catalase activity, and glutathione (GSH) content over control values. These changes are paralleled by a substantial increase in the lipid peroxidation potential of the liver and in the O2.-09 generation/SOD activity ratio, thus evidencing a higher oxidative stress status that correlates with the development of liver injury characterized by neutrophil infiltration and necrosis. Kupffer cell inactivation by GdCl3 suppresses liver injury in lindane/T3 -treated rats with normalization of altered oxidative stress-related parameters, excepting the reduction in the content of GSH and in catalase activity. It is concluded that lindane hepatotoxicity in hyperthyroid state, that comprises an enhancement in the oxidative stress status of the liver, is largely dependent on Kupffer cell function, which may involve generation of mediators leading to pro-oxidant and inflammatory processes. 相似文献
986.
Guang-rong Wang Howard K. Surks K. Mary Tang Yan Zhu Michael E. Mendelsohn Robert M. Blanton 《The Journal of biological chemistry》2013,288(34):24972-24983
NO, via its second messenger cGMP, activates protein kinase GI (PKGI) to induce vascular smooth muscle cell relaxation. The mechanisms by which PKGI kinase activity regulates cardiovascular function remain incompletely understood. Therefore, to identify novel protein kinase G substrates in vascular cells, a λ phage coronary artery smooth muscle cell library was constructed and screened for phosphorylation by PKGI. The screen identified steroid-sensitive gene 1 (SSG1), which harbors several predicted PKGI phosphorylation sites. We observed direct and cGMP-regulated interaction between PKGI and SSG1. In cultured vascular smooth muscle cells, both the NO donor S-nitrosocysteine and atrial natriuretic peptide induced SSG1 phosphorylation, and mutation of SSG1 at each of the two predicted PKGI phosphorylation sites completely abolished its basal phosphorylation by PKGI. We detected high SSG1 expression in cardiovascular tissues. Finally, we found that activation of PKGI with cGMP regulated SSG1 intracellular distribution. 相似文献
987.
988.
Barber MA Zhang T Gagne BA Van Ginderachter JA De Baetselier P Sentman CL 《Cancer immunology, immunotherapy : CII》2008,57(5):655-662
Background NK cell activity is regulated in part by inhibitory receptors that bind to MHC class I molecules. It is possible to enhance
NK cell cytotoxicity against tumor cells by preventing the interaction of these inhibitory receptors with their MHC class
I ligands.
Results In this study, we determined that Ly49G2 is an inhibitory receptor in AKR mice for self-MHC class I, and AKR Ly49G2 has an
identical sequence to BALB/c Ly49G2. Blockade of Ly49G2 receptors in vivo resulted in decreased growth of BW-Sp3 lymphoma
cells when the tumor cells were given i.v. but not when the tumor cells were inoculated into the flank forming a solid tumor.
However, NK cells were involved in inhibiting the growth of BW-Sp3 tumor cells in the flank.
Conclusion These data demonstrate that the effectiveness of inhibitory receptor blockade depends upon the tissue location of the tumor
cells. 相似文献
989.
Ca2+ mobilization elicited by simulation with brief pulses of high K + were monitored with confocal laser scanned microscopy in intact, guinea pig cardiac myocytes loaded with the calcium indicator fluo-3. Single wavelength ratioing of fluorescence images obtained after prolonged integration times revealed non-uniformities of intracellular Ca2+ changes across the cell, suggesting the presence of significant spatial Ca2+ gradients. Treatment with 20 μM ryanodine, an inhibitor of Ca2+ release from the SR, and 10 μM verapamil, a calcium channel blocker, reduced by 42% and 76% respectively the changes in [Ca2+]i elicited by membrane depolarization. The overall spatial distribution of [Ca2+]i changes appeared unchanged. Ca2+ transients recorded in the presence of verapamil and ryanodine (about 20% of the size of control responses), diminished in the presence of 50 μM 2-4 Dichlorbenzamil (DCB) or 5 mM nickel, two relatively specific inhibitors of the
exchange mechanism. Conversely, when the reversal potential of the
exchange was shifted to negative potentials by lowering [Na+]0 or by increasing [Na+]i by treatment with 20 μM monensin, the amplitude of these Ca2+ transients increased. Ca2+ transients elicited by membrane depolarization and largely mediated by reverse operation of Na+-Ca2+ exchange could be recorded in the presence of ryanodine, verapamil and monensin. These findings suggest that in intact guinea pig cardiac cells, Ca2+ influx through the
exchange mechanism activated by a membrane depolarization in the physiological range can be sufficient to play a significant role in excitation-contraction coupling. 相似文献
990.