全文获取类型
收费全文 | 29502篇 |
免费 | 2919篇 |
国内免费 | 2728篇 |
专业分类
耳鼻咽喉 | 106篇 |
儿科学 | 247篇 |
妇产科学 | 261篇 |
基础医学 | 3800篇 |
口腔科学 | 490篇 |
临床医学 | 1719篇 |
内科学 | 3105篇 |
皮肤病学 | 382篇 |
神经病学 | 1907篇 |
特种医学 | 578篇 |
外国民族医学 | 47篇 |
外科学 | 1756篇 |
综合类 | 7341篇 |
现状与发展 | 5篇 |
预防医学 | 877篇 |
眼科学 | 758篇 |
药学 | 4553篇 |
中国医学 | 2434篇 |
肿瘤学 | 4783篇 |
出版年
2024年 | 105篇 |
2023年 | 356篇 |
2022年 | 684篇 |
2021年 | 995篇 |
2020年 | 878篇 |
2019年 | 780篇 |
2018年 | 713篇 |
2017年 | 1002篇 |
2016年 | 1075篇 |
2015年 | 1368篇 |
2014年 | 1575篇 |
2013年 | 2118篇 |
2012年 | 1892篇 |
2011年 | 2135篇 |
2010年 | 1868篇 |
2009年 | 1747篇 |
2008年 | 1921篇 |
2007年 | 2003篇 |
2006年 | 1893篇 |
2005年 | 1825篇 |
2004年 | 1648篇 |
2003年 | 1492篇 |
2002年 | 1223篇 |
2001年 | 1192篇 |
2000年 | 905篇 |
1999年 | 580篇 |
1998年 | 469篇 |
1997年 | 307篇 |
1996年 | 179篇 |
1995年 | 107篇 |
1994年 | 47篇 |
1993年 | 12篇 |
1992年 | 15篇 |
1991年 | 11篇 |
1990年 | 3篇 |
1989年 | 10篇 |
1988年 | 1篇 |
1987年 | 6篇 |
1985年 | 3篇 |
1984年 | 2篇 |
1983年 | 2篇 |
1981年 | 1篇 |
1966年 | 1篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
271.
The induction of apoptosis by anticancer drugs and its relationship to stages of the cell cycle was studied in cells derived from a solid tumour; a highly malignant hamster fibrosarcoma (Met B). Asynchronously proliferating cells were treated with a wide variety of agents such as actinomycin-D, 1--D-arabinofuranosyl cytosine, camptothecin, cisplatin, cyclophosphamide, daunorubicin, 5-flurouracil, 6-mercaptopurine, hydroxyurea, ionomycin, methotrexate and vincristine. With the exception of cyclophosphamide and hydroxyurea, a 36 h exposure to these drugs resulted in inhibition of cell growth and apart from cyclophosphamide, hydroxyurea, 6-mercaptopurine and cisplatin the induction of apoptosis. Studies using a decreased concentration of drug and exp osure time (12 h) followed by examination of cells using flow cytometry indicated that most drugs were capable of affecting cell cycle progression without induction of apoptosis. However when cells were synchronised at G0/G1, S and G2/M phases and then exposed to these decreased concentrations of drug apart from 6MP an HU, apoptosis was observed and for the majority of drugs it took place in the same phase in which progression through the cell cycle was blocked by the drug. Cells synchronised in G0/G1 phase were more susceptible to methotrexate, whereas S-phase cells were more susceptible to camptothecin and 5-flurouracil and G2/M phase cells more susceptible to actinomycin D, 1--D-arabinofuranosyl cytosine, daunorubicin and cisplatin. In contrast, vincristine blocked cells in G2/M phase but exerted its apoptotic effect in S-phase cells, ionomycin had no effect on the cell cycle, but G2/M cells appeared to be more susceptible to the effect of this drug. These data indicate that entry into apoptosis by this fibrosarcoma may occur at any point in the cell cycle. They also demonstrate a correlation between the action of some anticancer drugs on the cell cycle and the subsequent induction of apoptosis which may be useful in chemotherapeutic design. 相似文献
272.
Estrogen increases intracellular p26Bcl-2 to p21Bax ratios and inhibits taxol-induced apoptosis of human breast cancer MCF-7 cells 总被引:7,自引:0,他引:7
Yue Huang Swapan Ray John C. Reed Ana Maria Ibrado Caroline Tang Amir Nawabi Kapil Bhalla 《Breast cancer research and treatment》1997,42(1):73-81
Recent studies have demonstrated that following estrogen ablation, estrogen responsive breast cancer cells undergo apoptosis. In addition, estrogen receptor (ER) expression has been strongly correlated with the expression of the bcl-2 gene product, p26Bcl-2 protein, which is known to inhibit apoptosis. In the present studies, we investigated whether estrogen affects the intracellular levels of p26Bcl-2 and thereby modulates taxol-induced apoptosis of estrogen responsive human breast cancer MCF-7 cells. Transfer of MCF-7 cells to a culture-medium without estrogens reduced their intracellular p26Bcl-2 levels by 50%. Inclusion of 0.1 M estradiol in the medium produced approximately a four-fold increase in p26Bcl-2, but not p29Bcl-xL or p21Bax levels; the expression of the c-myc and mdr-1 genes remained unchanged. Estradiol-induced four-fold increase in the ratio of the p26Bcl-2 to p21Bax levels caused a significant decline in the lethal, kilobase size DNA fragments of apoptosis, which had resulted when MCF-7 cells were cultured in a medium without estrogen. In addition, in MCF-7 cells, estradiol-induced increase in the intracellular p26Bcl-2 to p21Bax ratios was associated with a significant reduction in the large-sized DNA fragmentation induced by treatment with taxol. The increased ratios also protected MCF-7 cells against taxol-mediated cytotoxicity as assessed by the MTT assay. These results suggest that by modulating p26Bcl-2 levels, estrogens may affect the antitumor activity of taxol and potentially of other anti-breast cancer drugs against estrogen responsive human breast cancer cells. 相似文献
273.
Infection with the human immunodeficiency virus (HIV) causes gradual depletion of CD4+ T helper lymphocytes and destruction
of the lymphoid tissue, which ultimately leads to a fatal defect of the cellular immune system. Paramount to the understanding
of the pathogenesis of HIV infection is to elucidate the mechanism which underlies the loss of T helper cells. Various ideas
have been proposed in order to explain this issue. Several hypotheses have focused on the role of the envelope glycoprotein
in this process. This review summarizes the data obtained and concepts proposed regarding the involvement of the HIV glycoprotein
in the pathology of CD4+ T cell depletion.
This work was supported by the Deutsche Forschungsgemeinschaft, the Bundesministerium fur Bildung, Wissenschaft, Forschung
und Technologie and the Stifterverband für die Deutsche Wissenschaft 相似文献
274.
Tumor necrosis factor-{alpha} up-regulates Bcl-2 expression and decreases calcium-dependent apoptosis in human B cell lines 总被引:7,自引:0,他引:7
Genestier Laurent; Bonnefoy-Berard Nathalie; Rouault Jean-Pierre; Flacher Monique; Revillard Jean-Pierre 《International immunology》1995,7(4):533-540
Group I and Epstein–Barr virus-negative Burkitt's lymphomacell lines and the B104 lymphoma cell line which expresses aphenotype of immature B cells undergo apoptosis after cross-linkingof their surface Ig receptors or after exposure to a calciumionophore. We show here that tumor necrosis factor (TNF)- protectsthese B cell lines against Ca2+-dependent apoptosis. Protectionwas associated with up-regulatlon of bcl-2 mRNA and proteinexpression. The increase of Bcl-2 expression induced by TNF-was inhibited by chelerythrine, a specific inhibitor of proteinkinase C (PKC), suggesting that Bcl-2 expression was dependenton PKC activation. Furthermore, we show that phorbol estersand cyclosporin A (CsA), which prevent Ca2+-dependent apoptosis,up-regulated Bcl-2 expression. The effect of CsA on Bcl-2 expressionis controlled by calcineurin since we have shown that FK506but not rapamycin had the same effect on Bcl-2 expression, whereasokadaic acid, an inhibitor of phosphatases 1, 2A and 2C, wasineffective. These data provide direct evidence that TNF- preventsCa2+-dependent apoptosis by a Bcl-2-dependent mechanism mediatedby PKC. 相似文献
275.
Signals and molecular pathways involved in apoptosis, with special emphasis on human endometrium 总被引:7,自引:1,他引:6
Apoptosis is a selective process for deletion of cells in variousbiological systems. This event, similar to proliferation, istightly regulated, with both processes playing essential rolesin the homeostasis of renewable tissues. In human endometrium,proliferation and apoptosis occur at opposing poles of the menstrualcycle. The proliferative phase is marked by rapid growth ofthe endometrial epithelial lining, whereas progressive increasein apoptosis in this tissue is the hallmark of the secretoryand menstrual phases. The purpose of this review is to highlightsome of the signals and molecular events which are associatedwith and that may participate in apoptosis. This is followedby a review of the current literature regarding apoptosis inhuman endometrium. 相似文献
276.
AS_2O_3对消化道肿瘤细胞凋亡作用的研究 总被引:4,自引:0,他引:4
目的研究AS3O3对10种消化道肿瘤细胞株的致凋亡作用。方法采用形态学观察、流式细胞仪检测及DNA电泳分析。结果发现两株细胞经AS2O3作用后有明显凋亡,三株细胞无凋亡,其余有少量凋亡。结论AS2O3对不同的消化道肿瘤细胞有不同的作用,提示AS2O3对不同细胞的致凋亡作用可能存在不同的机理。 相似文献
277.
The absence or low levels of adenosine deaminase (ADA) in humans result in severe combined immunodeficiency (SCID), which is characterized by hypoplastic thymus, T lymphocyte depletion and autoimmunity. Deficiency of ADA causes increased levels of both intracellular and extracellular adenosine, although only the intracellular lymphotoxicity of accumulated adenosine is considered in the pathogenesis of ADA SCID. It is shown that extracellular but not intracellular adenosine selectively inhibits TCR-triggered up-regulation of activation markers and apoptotic events in thymocytes under conditions of ADA deficiency. The effects of intracellular adenosine are dissociated from effects of extracellular adenosine in experiments using an adenosine transporter blocker. We found that prevention of toxicity of intracellular adenosine led to survival of TCR-cross-linked thymocytes in long-term (4 days) assays, but it was not sufficient for normal T cell differentiation under conditions of inhibited ADA. Surviving TCR-cross-linked thymocytes had a non-activated phenotype due to extracellular adenosine-mediated, TCR-antagonizing signaling. Taken together the data suggest that both intracellular toxicity and signaling by extracellular adenosine may contribute to pathogenesis of ADA SCID. Accordingly, extracellular adenosine may act on thymocytes, which survived intracellular toxicity of adenosine during ADA deficiency by counteracting TCR signaling. This, in turn, could lead to failure of positive and negative selection of thymocytes, and to additional elimination of thymocytes or autoimmunity of surviving T cells. 相似文献
278.
雄黄诱导K562/ADM细胞凋亡的研究 总被引:11,自引:0,他引:11
探讨雄黄诱导多药耐药细胞K562/ADM细胞凋亡的能力,并初步探讨其分子机制,方法:采用荧光标记形态学观察,流式细胞仪进行DNA分析及测定细胞表面p-gp的表达。结果显示:雄黄能明显诱导K562/ADM细胞凋亡,且在48h后p-gp的表达下调。 相似文献
279.
ThecoronaryarterycomplicationcouldbefoundinalmostalcasesofKawasakidisease[1].Ithasrecentlybeenshownthatplatelet-derivedgrowth... 相似文献
280.
Apoptosishasbeenintensivelystudiedinhepatobiliarydiseases.However,dataabouttherelationshipbetweenlivercirho-sisandapoptosisis... 相似文献