全文获取类型
收费全文 | 82480篇 |
免费 | 5787篇 |
国内免费 | 3734篇 |
专业分类
耳鼻咽喉 | 348篇 |
儿科学 | 1481篇 |
妇产科学 | 846篇 |
基础医学 | 13029篇 |
口腔科学 | 1664篇 |
临床医学 | 6915篇 |
内科学 | 14391篇 |
皮肤病学 | 1031篇 |
神经病学 | 7729篇 |
特种医学 | 1316篇 |
外国民族医学 | 15篇 |
外科学 | 4834篇 |
综合类 | 13928篇 |
现状与发展 | 22篇 |
预防医学 | 4950篇 |
眼科学 | 967篇 |
药学 | 10553篇 |
11篇 | |
中国医学 | 2590篇 |
肿瘤学 | 5381篇 |
出版年
2024年 | 180篇 |
2023年 | 874篇 |
2022年 | 2208篇 |
2021年 | 3011篇 |
2020年 | 2410篇 |
2019年 | 2062篇 |
2018年 | 2033篇 |
2017年 | 2345篇 |
2016年 | 2669篇 |
2015年 | 3016篇 |
2014年 | 5070篇 |
2013年 | 5680篇 |
2012年 | 5377篇 |
2011年 | 6000篇 |
2010年 | 4755篇 |
2009年 | 4614篇 |
2008年 | 4748篇 |
2007年 | 4600篇 |
2006年 | 4127篇 |
2005年 | 3888篇 |
2004年 | 3177篇 |
2003年 | 2705篇 |
2002年 | 2076篇 |
2001年 | 1782篇 |
2000年 | 1540篇 |
1999年 | 1318篇 |
1998年 | 1224篇 |
1997年 | 1072篇 |
1996年 | 916篇 |
1995年 | 729篇 |
1994年 | 700篇 |
1993年 | 587篇 |
1992年 | 505篇 |
1991年 | 475篇 |
1990年 | 394篇 |
1989年 | 311篇 |
1988年 | 295篇 |
1987年 | 286篇 |
1986年 | 255篇 |
1985年 | 361篇 |
1984年 | 317篇 |
1983年 | 211篇 |
1982年 | 244篇 |
1981年 | 191篇 |
1980年 | 164篇 |
1979年 | 109篇 |
1978年 | 91篇 |
1977年 | 77篇 |
1976年 | 67篇 |
1975年 | 54篇 |
排序方式: 共有10000条查询结果,搜索用时 0 毫秒
151.
Surojit Paul Peter Olausson Deepa V Venkitaramani Irina Ruchkina Timothy D Moran Natalie Tronson Evan Mills Shawn Hakim Michael W Salter Jane R Taylor Paul J Lombroso 《Neuropsychopharmacology》2007,61(9):1049-1061
BACKGROUND: Formation of long-term memories is critically dependent on extracellular-regulated kinase (ERK) signaling. Activation of the ERK pathway by the sequential recruitment of mitogen-activated protein kinases is well understood. In contrast, the proteins that inactivate this pathway are not as well characterized. METHODS: Here we tested the hypothesis that the brain-specific striatal-enriched protein tyrosine phosphatase (STEP) plays a key role in neuroplasticity and fear memory formation by its ability to regulate ERK1/2 activation. RESULTS: STEP co-localizes with the ERKs within neurons of the lateral amygdala. A substrate-trapping STEP protein binds to the ERKs and prevents their nuclear translocation after glutamate stimulation in primary cell cultures. Administration of TAT-STEP into the lateral amygdala (LA) disrupts long-term potentiation (LTP) and selectively disrupts fear memory consolidation. Fear conditioning induces a biphasic activation of ERK1/2 in the LA with an initial activation within 5 minutes of training, a return to baseline levels by 15 minutes, and an increase again at 1 hour. In addition, fear conditioning results in the de novo translation of STEP. Inhibitors of ERK1/2 activation or of protein translation block the synthesis of STEP within the LA after fear conditioning. CONCLUSIONS: Together, these data imply a role for STEP in experience-dependent plasticity and suggest that STEP modulates the activation of ERK1/2 during amygdala-dependent memory formation. The regulation of emotional memory by modulating STEP activity may represent a target for the treatment of psychiatric disorders such as posttraumatic stress disorder (PTSD), panic, and anxiety disorders. 相似文献
152.
目的 研究慢性"炎症性"肺动脉高压大鼠在肺动脉高压形成过程中肺动脉蛋白激酶C(PKC)亚型的表达.方法 建立野百合碱诱导的慢性"炎症性"肺动脉高压大鼠模型,应用Western blot技术检测肺动脉高压形成过程中大鼠肺动脉四种PKC亚型(PKCα、PKCβⅡ、PKCδ和PKCε)的表达变化.结果 PKCα、PKCβⅡ和PKCδ亚型在正常和肺动脉高压大鼠肺动脉中均有表达,而PKCε亚型未检测到.在肺动脉高压形成过程中,大鼠肺动脉胞浆和胞膜组分表达的PKCα均逐渐上升,到第14天达到高峰后略有下降,且胞膜表达量的升高远比胞浆明显.胞浆PKCβⅡ和PKCδ表达量均在第8天达最高,而胞膜中二者均表现出持续升高的趋势.结论 PKCα、PKCβⅡ和PKCδ亚型可能参与了慢性"炎症性"肺动脉高压的形成,其表达变化可能与其转位有关. 相似文献
153.
Pharmacologic preconditioning effects: Prostaglandin E1 induces heat-shock proteins immediately after ischemia/reperfusion of the mouse liver 总被引:1,自引:0,他引:1
Ken-ichi Matsuo M.D. Shinji Togo M.D. Ph.D. Hitoshi Sekido M.D. Ph.D. Tomoyuki Morita M.D. Ph.D. Masako Kamiyama Ph.D. Daisuke Morioka M.D. Ph.D. Toru Kubota M.D. Ph.D. Yasuhiko Miura M.D. Ph.D. Kuniya Tanaka M.D. Ph.D. Takashi Ishikawa M.D. Ph.D. Yasushi Ichikawa M.D. Ph.D. Itaru Endo M.D. Ph.D. Hitoshi Goto M.D. Ph.D. Hiroyuki Nitanda M.D. Ph.D. Yasushi Okazaki M.D. Ph.D. Yoshihide Hayashizaki M.D. Ph.D. Hiroshi Shimada M.D. Ph.D. 《Journal of gastrointestinal surgery》2005,9(6):758-768
Prostaglandin E1 (PGE1) has several potential therapeutic effects, including cytoprotection, vasodilation, and inhibition of platelet aggregation. This study investigates the protective action of PGE1 against hepatic ischemia/reperfusion injury in vivo using a complementary DNA microarray. PGE1 or saline was continuously administered intravenously to mice in which the left lobe of the liver was made ischemic for 30 minutes and then reperfused. Livers were harvested 0, 10, and 30 minutes postreperfusion. Messenger RNA was extracted, and the samples were labeled with two different fluorescent dyes and hybridized to the RIKEN set of 18,816 full-length enriched mouse complementary DNA microarrays. Serum alanine aminotransferase and aspartate aminotransferase levels at 180 minutes postreperfusion were significantly lower in the PGE1-treated group than in the saline-treated group. The cDNA microarray analysis revealed that the genes encoding heat-shock protein (HSP) 70, glucose-regulated protein 78, HSP86, and glutathione S-transferase were upregulated at the end of the ischemic period (0 minutes postreperfusion) in the PGE1 group. Our results suggested that PGE1 induces HSPs immediately after ischemia reperfusion. HSPs might therefore play an important role in the protective effects of PGE1 against ischemia/reperfusion injury of the liver. 相似文献
154.
155.
穹窿体是真核细胞中的核糖核蛋白颗粒,由肺耐药蛋白、穹窿体多聚腺苷二磷酸聚合酶、端粒酶相关蛋白和穹窿体RNA构成,其主要成分为肺耐药蛋白。肺耐药蛋白是介导肿瘤多药耐药的蛋白之一,可能与肿瘤的治疗效果和临床预后相关。穹窿体可能通过介导药物转运或者信号转导引起肿瘤的多药耐药。文章介绍了穹窿体的结构、成分及其介导多药耐药机制研究的新进展。 相似文献
156.
目的:探讨心肌营养素1(cardiotrophin 1,CT1)/破伤风毒素重链C端片段(tentanus toxin C fragment,TTC)(CT1/TTC)融合蛋白的构建及其对大鼠嗜铬细胞瘤(pheochromocytoma,PC12)细胞的靶向性。方法:采用聚合酶链式反应(PCR)、T-A克隆等分子生物学方法构建CT1/TTC融合蛋白。体外培养PC12细胞,并将CT1/TTC融合蛋白与PC12细胞共培养,红色荧光免疫组化染色后在激光共聚焦显微镜下观察融合蛋白能否在TTC的靶向作用下进入PC12细胞。结果:成功构建了CT1/TTC融合蛋白,测序显示融合基因序列正确,免疫组化染色结果显示融合蛋白能够进入PC12细胞,并发出红色荧光。结论:采用PCR和T-A克隆等分子生物学方法能成功构建CT1/TTC融合蛋白.并且TTC能够将CT1靶向进入PC12细胞。 相似文献
157.
Yasushi Nishihira Chun‐Feng Tan Junko Hirato Junichi Yoshimura Kenichi Nishiyama Hideaki Takahashi Yukihiko Fujii Hitoshi Takahashi 《Neuropathology》2007,27(6):551-555
Two embryonal CNS tumors, atypical teratoid/rabdoid tumor (AT/RT) and primitive neuroectodermal tumor (PNET), may be confused with each other and misdiagnosed. Here we report an infant with a congenital supratentorial tumor, which was detected by fetal MRI at 37 weeks gestation. On routine histological examination, the tumor was composed mainly of small undifferentiated cells, among which many rhabdoid cells and occasional sickle‐shaped embracing cells were observed. No mesenchymal or epithelial areas were evident. Our impression was that the tumor was an atypical example of AT/RT. Immunohistochemically, almost all the tumor cells were strongly positive for vimentin. However, epithelial membrane antigen was notably negative, and most of the tumor cell nuclei were clearly positive for INI1. In addition, many tumor cells were positive for neurofilament protein. There were also occasional small areas containing many tumor cells positive for glial fibrillary acidic protein. Finally, a diagnosis of PNET, with a rhabdoid phenotype and expression of neuronal and glial markers, was made. In the present case, application of INI1 immunostaining was very helpful for distinguishing PNET from AT/RT. 相似文献
158.
人Heparanase基因真核和原核表达载体的构建及融合蛋白的表达 总被引:1,自引:1,他引:0
目的:构建人Heparanase基因的真核、原核表达载体,大肠杆菌表达其融合蛋白.方法:采用反转录.聚合酶链反应从人肝癌细胞株HepG2cDNA中,分别扩增出Heparanase编码基因,用限制性内切酶BamHI消化后,插入真核表达载体pcDNA3.1中,经酶切鉴定与测序证实后,连接成包括完整的人Heparanase基因ORF区的真核表达载体,以亚克隆法构建于原核表达载体pRSET的相应酶切位点,转化大肠杆菌BL21菌株,异丙基β-D硫代半乳糖苷(IPTG)诱导产生融合蛋白.结果:构建的人Heparanase基因表达载体经序列测定证实,与GenBank登录结果完全一致;双酶切鉴定证实,克隆基因正确插入载体pcDNA3.1及pRSET;SDS-PAGE证实融合蛋白表达成功.结论:成功构建了人Heparanase基因真核、原核表达载体,成功正确表达了6His/Heparanase融合蛋白 相似文献
159.
胰岛素和睾酮对Ishikawa细胞葡萄糖转运蛋白4表达的影响 总被引:1,自引:0,他引:1
目的探讨胰岛素(INS)和睾酮(T)对多囊卵巢综合征(PCOS)子宫内膜腺上皮细胞生长的影响和葡萄糖转运蛋白4(GLUT4)表达的调节机制。方法体外培养Ishikawa细胞,予不同浓度INS(90、60、30、3、0.3 U/L)或T(10-3、10-4、10-5、10-6、10-7mmol/ml)刺激Ishikawa细胞48 h,MTT法检测INS、T对Ishikawa细胞生长的作用;免疫细胞化学检测GLUT4蛋白在Ishikawa细胞定位表达;分别以30 U/L INS和10-5mmol/ml T刺激Ishikawa细胞24和48 h,逆转录聚合酶链反应(RT-PCR)方法测定INS和T对Ishikawa细胞GLUT4 mRNA表达的影响。结果(1)不同浓度的INS均可促进Ishikawa细胞的生长,随着INS浓度的增加,INS促进Ishikawa细胞生长作用越强,INS浓度自0.3~30 U/L时,Ishikawa细胞生长依次加强,与对照组相比均有显著性差异(P<0.01)。INS浓度达60、90 U/L时,细胞生长状况与INS浓度为30 U/L相似。不同浓度的T均可抑制Ishikawa细胞的生长,随着T浓度的增加,T抑制Ishikawa细胞生长作用越明显。T浓度自10-7、10-6、10-5mmol/ml,Ishikawa细胞生长依次减弱,与对照组相比均有显著性差异(P<0.01,P<0.05),T浓度达10-4、10-3mmol/ml时,细胞生长抑制状况与T浓度10-5mg/ml相似。(2)GLUT4蛋白,定位表达于Ishikawa细胞的细胞浆内。(3)Ishikawa细胞中GLUT4 mRNA表达,在INS组和T组均较对照组减弱(P<0.01,P<0.05),INS组比T组减弱更明显(P<0.05),且INS和T作用24和48 h GLUT4 mRNA表达无显著性差异(P>0.05)。结论不同浓度INS和T均可影响Ishikawa细胞生长,并降低GLUT4 mRNA的表达,推测PCOS高胰岛素、高雄激素血症的病理生理特性有可能影响子宫内膜的代谢过程,与子宫内膜的病变相关。 相似文献
160.
Tetsuji Fujita Katsuhiko Yanaga 《Langenbeck's archives of surgery / Deutsche Gesellschaft fur Chirurgie》2007,392(2):127-130
BACKGROUND: Although there is increasing evidence suggesting that the vagus nerve functions as a connector between the nervous and immune systems in animals, little is known about the role of the vagus nerve in postoperative acute phase response in humans. MATERIALS AND METHODS: The extent of fever and acute phase protein response and the production of inflammatory cytokine during the early postoperative period were compared among the patients who had undergone total gastrectomy including truncal vagotomy (n = 13), those having distal gastrectomy with division of vagal branches (n = 14), and the patients with vagal nerve preserving gastrectomy (n = 12). RESULTS: There was no significant difference in serum levels of C-reactive protein, alpha-1-antirypsin, and interleukin-6 among the three groups. Also, postoperative maximum body temperature was similar. CONCLUSIONS: Vagotomy did not influence acute phase response after gastric cancer surgery. A multipathway mechanism for acute phase response including the induction of fever is suggested. 相似文献