全文获取类型
收费全文 | 2732篇 |
免费 | 195篇 |
国内免费 | 61篇 |
专业分类
耳鼻咽喉 | 9篇 |
儿科学 | 90篇 |
妇产科学 | 136篇 |
基础医学 | 324篇 |
口腔科学 | 40篇 |
临床医学 | 337篇 |
内科学 | 785篇 |
皮肤病学 | 28篇 |
神经病学 | 170篇 |
特种医学 | 154篇 |
外科学 | 272篇 |
综合类 | 28篇 |
一般理论 | 2篇 |
预防医学 | 297篇 |
眼科学 | 22篇 |
药学 | 103篇 |
中国医学 | 4篇 |
肿瘤学 | 187篇 |
出版年
2023年 | 18篇 |
2022年 | 16篇 |
2021年 | 53篇 |
2020年 | 24篇 |
2019年 | 52篇 |
2018年 | 69篇 |
2017年 | 61篇 |
2016年 | 60篇 |
2015年 | 54篇 |
2014年 | 110篇 |
2013年 | 127篇 |
2012年 | 153篇 |
2011年 | 176篇 |
2010年 | 97篇 |
2009年 | 96篇 |
2008年 | 163篇 |
2007年 | 178篇 |
2006年 | 111篇 |
2005年 | 124篇 |
2004年 | 99篇 |
2003年 | 100篇 |
2002年 | 84篇 |
2001年 | 77篇 |
2000年 | 58篇 |
1999年 | 82篇 |
1998年 | 55篇 |
1997年 | 48篇 |
1996年 | 44篇 |
1995年 | 34篇 |
1994年 | 43篇 |
1993年 | 37篇 |
1992年 | 51篇 |
1991年 | 44篇 |
1990年 | 24篇 |
1989年 | 51篇 |
1988年 | 36篇 |
1987年 | 33篇 |
1986年 | 25篇 |
1985年 | 25篇 |
1984年 | 18篇 |
1983年 | 13篇 |
1982年 | 19篇 |
1981年 | 15篇 |
1980年 | 17篇 |
1979年 | 17篇 |
1978年 | 13篇 |
1976年 | 17篇 |
1975年 | 8篇 |
1973年 | 9篇 |
1969年 | 7篇 |
排序方式: 共有2988条查询结果,搜索用时 31 毫秒
41.
42.
Parker JC McPherson RK Andrews KM Levy CB Dubins JS Chin JE Perry PV Hulin B Perry DA Inagaki T Dekker KA Tachikawa K Sugie Y Treadway JL 《Diabetes》2000,49(12):2079-2086
Peptidic glucagon antagonists have been shown to lower blood glucose levels in diabetic models (1-3), but attempts to identify small molecular weight glucagon receptor-binding antagonists have met with little success. Skyrin, a fungal bisanthroquinone, exhibits functional glucagon antagonism by uncoupling the glucagon receptor from adenylate cyclase activation in rat liver membranes (1). We have examined the effects of skyrin on cells transfected with the human glucagon receptor and on isolated rat and human hepatocytes. The skyrin used was isolated from Talaromyces wortmanni American Type Culture Collection 10517. In rat hepatocytes, skyrin (30 micromol/l) inhibited glucagon-stimulated cAMP production (53%) and glucose output (IC50 56 micromol/l). There was no detectable effect on epinephrine or glucagon-like peptide 1 (GLP-1) stimulation of these parameters, which demonstrates skyrin's selective activity. Skyrin was also evaluated in primary cultures of human hepatocytes. Unlike cell lines, which are largely unresponsive to glucagon, primary human hepatocytes exhibited glucagon-dependent cAMP production for 14 days in culture (EC50 10 nmol/l). Skyrin (10 micromol/l) markedly reduced glucagon-stimulated cAMP production (55%) and glycogenolysis (27%) in human hepatocytes. The inhibition of glucagon stimulation was a specific property displayed by skyrin and oxyskyrin but not shared by other bisanthroquinones. Skyrin is the first small molecular weight nonpeptidic agent demonstrated to interfere with the coupling of glucagon to adenylate cyclase independent of binding to the glucagon receptor. The data presented in this study indicate that functional uncoupling of the human glucagon receptor from cAMP production results in metabolic effects that could reduce hepatocyte glucose production and hence alleviate diabetic hyperglycemia. 相似文献
43.
Induction of p53 up-regulated modulator of apoptosis messenger RNA by chemotherapeutic treatment of locally advanced breast cancer. 总被引:1,自引:0,他引:1
Rutger Middelburg Richard R de Haas Henk Dekker Ron M Kerkhoven Paula R Pohlmann Adolfo Fuentes-Alburo Alejandro Mohar Herbert M Pinedo Jan Lankelma 《Clinical cancer research》2005,11(5):1863-1869
PURPOSE: In biopsies of patients with locally advanced breast cancer, we investigated the in vivo changes of the gene expression pattern induced by chemotherapy to find genes that are potentially responsible for the efficacy of the drug. EXPERIMENTAL DESIGN: Early cellular responses to chemotherapy-induced damage, both in vivo and in vitro, were investigated by analyzing chemotherapy-induced changes in gene expression profiles. Core biopsies were taken from nine patients with locally advanced breast cancer, before and at 6 hours after initiation of doxorubicin-based chemotherapy. Both samples were cohybridized on the same microarray containing 18,000 cDNA spots. RESULTS: The analysis revealed marked differences in gene expression profile between treated and untreated samples. The gene which was most frequently found to be differentially expressed was p53 up-regulated modulator of apoptosis (PUMA). This gene was up-regulated in eight of nine patients with an average factor of 1.80 (range, 1.36-2.73). In vitro MCF-7 breast cancer cells exposed to clinically achievable doxorubicin concentrations for 6 hours revealed marked induction of PUMA mRNA, as well. CONCLUSIONS: This is the first report describing PUMA mRNA to be up-regulated as a response to chemotherapy in patients. Because PUMA is a known member of the family of BH3-only proapoptotic proteins, this finding suggests PUMA's potential importance for the response to anticancer drugs. 相似文献
44.
B. Guigas J. E. de Leeuw van Weenen N. van Leeuwen A. M. Simonis‐Bik T. W. van Haeften G. Nijpels J. J. Houwing‐Duistermaat M. Beekman J. Deelen L. M. Havekes B. W. J. H. Penninx N. Vogelzangs E. van ‘t Riet A. Dehghan A. Hofman J. C. Witteman A. G. Uitterlinden N. Grarup T. Jørgensen D. R. Witte T. Lauritzen T. Hansen O. Pedersen J. Hottenga J. A. Romijn M. Diamant M. H. H. Kramer R. J. Heine G. Willemsen J. M. Dekker E. M. Eekhoff H. Pijl E. J. de Geus P. E. Slagboom L. M. ‘t Hart 《Diabetic medicine》2014,31(8):1001-1008
45.
46.
Jin Huk Choi Joe Dekker Stephen C. Schafer Jobby John Craig E. Whitfill Christopher S. Petty Eid E. Haddad Maria A. Croyle 《Clinical and Vaccine Immunology : CVI》2012,19(1):84-95
The immune response to recombinant adenoviruses is the most significant impediment to their clinical use for immunization. We test the hypothesis that specific virus-antibody combinations dictate the type of immune response generated against the adenovirus and its transgene cassette under certain physiological conditions while minimizing vector-induced toxicity. In vitro and in vivo assays were used to characterize the transduction efficiency, the T and B cell responses to the encoded transgene, and the toxicity of 1 × 1011 adenovirus particles mixed with different concentrations of neutralizing antibodies. Complexes formed at concentrations of 500 to 0.05 times the 50% neutralizing dose (ND50) elicited strong virus- and transgene-specific T cell responses. The 0.05-ND50 formulation elicited measurable anti-transgene antibodies that were similar to those of virus alone (P = 0.07). This preparation also elicited very strong transgene-specific memory T cell responses (28.6 ± 5.2% proliferation versus 7.7 ± 1.4% for virus alone). Preexisting immunity significantly reduced all responses elicited by these formulations. Although lower concentrations (0.005 and 0.0005 ND50) of antibody did not improve cellular and humoral responses in naïve animals, they did promote strong cellular (0.005 ND50) and humoral (0.0005 ND50) responses in mice with preexisting immunity. Some virus-antibody complexes may improve the potency of adenovirus-based vaccines in naïve individuals, while others can sway the immune response in those with preexisting immunity. Additional studies with these and other virus-antibody ratios may be useful to predict and model the type of immune responses generated against a transgene in those with different levels of exposure to adenovirus. 相似文献
47.
48.
49.
50.