全文获取类型
收费全文 | 124596篇 |
免费 | 11069篇 |
国内免费 | 7953篇 |
专业分类
耳鼻咽喉 | 1079篇 |
儿科学 | 1592篇 |
妇产科学 | 1663篇 |
基础医学 | 13717篇 |
口腔科学 | 2126篇 |
临床医学 | 15922篇 |
内科学 | 17723篇 |
皮肤病学 | 1335篇 |
神经病学 | 6186篇 |
特种医学 | 4428篇 |
外国民族医学 | 46篇 |
外科学 | 11466篇 |
综合类 | 22973篇 |
现状与发展 | 22篇 |
一般理论 | 13篇 |
预防医学 | 9553篇 |
眼科学 | 3323篇 |
药学 | 13914篇 |
133篇 | |
中国医学 | 6861篇 |
肿瘤学 | 9543篇 |
出版年
2024年 | 380篇 |
2023年 | 1583篇 |
2022年 | 4190篇 |
2021年 | 5511篇 |
2020年 | 4314篇 |
2019年 | 3612篇 |
2018年 | 3814篇 |
2017年 | 3765篇 |
2016年 | 3396篇 |
2015年 | 5369篇 |
2014年 | 6788篇 |
2013年 | 6686篇 |
2012年 | 9934篇 |
2011年 | 10738篇 |
2010年 | 7469篇 |
2009年 | 6079篇 |
2008年 | 7728篇 |
2007年 | 7259篇 |
2006年 | 6777篇 |
2005年 | 6185篇 |
2004年 | 4596篇 |
2003年 | 4202篇 |
2002年 | 3664篇 |
2001年 | 2889篇 |
2000年 | 2722篇 |
1999年 | 2603篇 |
1998年 | 1650篇 |
1997年 | 1630篇 |
1996年 | 1254篇 |
1995年 | 1168篇 |
1994年 | 1008篇 |
1993年 | 598篇 |
1992年 | 680篇 |
1991年 | 615篇 |
1990年 | 488篇 |
1989年 | 431篇 |
1988年 | 355篇 |
1987年 | 342篇 |
1986年 | 258篇 |
1985年 | 212篇 |
1984年 | 142篇 |
1983年 | 90篇 |
1982年 | 66篇 |
1981年 | 49篇 |
1980年 | 36篇 |
1979年 | 46篇 |
1978年 | 21篇 |
1974年 | 22篇 |
1973年 | 19篇 |
1966年 | 18篇 |
排序方式: 共有10000条查询结果,搜索用时 156 毫秒
41.
目的建立中国成年患者的替考拉宁(teicoplanin,TEC)群体药动学(population pharmacokinetics,PPK)模型,考察TEC药动学参数的影响因素。方法前瞻性收集139例革兰阳性球菌感染患者静脉注射TEC后的222份常规监测血药浓度和相关信息,采用一级消除的一室模型进行数据拟合,并应用非线性混合效应模型(nonlinear mixed effect model,NONMEM)程序建立PPK模型。采用Bootstrap、正态预测分布误差法(normalized predictive distribution error,NPDE)进行最终模型评价。利用蒙特卡洛模拟法对给药方案进行优化。结果确定了肌酐清除率(creatinine clearance,CLcr)、白蛋白(albumin,ALB)为影响TEC清除率的主要因素。最终模型为:CL(L·h^-1)=1.24×(CLcr/77)0.564×31/ALB;V(L)=69.2。验证表明,模型稳定、有效,且有较好的预测效能。对于不同ALB和CLcr的多数患者起始负荷剂量400 mg/q12h,iv,3次,维持剂量400~800 mg·d^-1的给药方案可达有效治疗谷浓度。严重感染者需调整负荷剂量至800 mg/q12h,iv,3次,维持剂量400~800 mg·d^-1的给药方案来确保血药浓度达到15 mg·L^-1以上。结论本实验报道了CLcr、ALB对TEC清除率有显著影响,所建模型对TEC在中国成人患者中实现个体化给药具有重要应用价值。 相似文献
42.
目的探讨针刺京骨穴联合推拿治疗背肌筋膜炎的临床疗效。方法将2016年10月—2018年10月收治的背肌筋膜炎患者86例纳入研究,采用随机数字表法分组。对照组43例予以推拿治疗,观察组43例予以针刺京骨穴联合推拿治疗。比较2组患者的治疗总有效率、VAS评分及Oswestry功能障碍指数、痊愈所用时间。结果观察组治疗总有效率为95.3%,而对照组仅为81.4%,差异有统计学意义(P<0.05);2组治疗后VAS评分、Oswestry功能障碍指数均有下降,观察组上述指标低于对照组,差异有统计学意义(P<0.05);观察组痊愈所用时间短于对照组,差异有统计学意义(P<0.05)。结论针刺京骨穴联合推拿治疗背肌筋膜炎的临床疗效突出,可缓解背部疼痛、恢复功能活动,并缩短了愈合时间,提高了生活质量,值得一定的临床推广。 相似文献
43.
Michael A. Gibney David Fitz-Patrick David C. Klonoff Shahista Whooley Betty Lu Wen Yue 《Current medical research and opinion》2020,36(10):1591-1600
Abstract
Objective
Two similarly designed studies compared user experiences with a second-generation extra-thin-wall, 5-bevel 32?G?×?4?mm pen needle (PN) with redesigned hub versus four thinner commercially available PNs. 相似文献44.
45.
Yaobin Ouyang Gongmeizi Liu Wenting Xu Zhen Yang Nianshuang Li Chuan Xie Chun Zhou Jiang Chen Yin Zhu Junbo Hong Nonghua Lu 《Oncology Letters》2021,21(2)
Helicobacter pylori (H. pylori) is a main risk factor for gastric cancer (GC). Epithelial-mesenchymal transition (EMT) is involved in the development and progression of H. pylori-associated GC. However, the exact molecular mechanism of this process remains unclear. The AKT/GSK3β signaling pathway has been demonstrated to promote EMT in several types of cancer. The present study investigated whether H. pylori infection induced EMT, and promoted the development and metastasis of cancer in the normal gastric mucosa, and whether this process was dependent on AKT activation. The expression levels of the EMT-associated proteins, including E-cadherin and N-cadherin, were determined in 165 gastric mucosal samples of different disease stages by immunohistochemical analysis. The expression levels of E-cadherin, N-cadherin, AKT, phosphorylated (p-)AKT (Ser473), GSK3β and p-GSK3β (Ser9) were further determined in H. pylori-infected Mongolian gerbil gastric tissues and cells co-cultured with H. pylori by immunohistochemical analysis and western blotting. The results indicated that the expression levels of the epithelial marker E-cadherin were decreased, whereas the expression levels of the mesenchymal marker N-cadherin were increased during gastric carcinogenesis. Their expression levels were associated with H. pylori infection. Furthermore, H. pylori infection resulted in downregulation of E-cadherin expression and upregulation of N-cadherin expression in Mongolian gerbils and GES-1 cells. In addition, an investigation of the associated mechanism of action revealed that p-AKT (Ser473) and p-GSK3β (Ser9) were activated in GES-1 cells following co-culture with H. pylori. Furthermore, following pretreatment of the cells with the AKT inhibitor VIII, the expression levels of E-cadherin, N-cadherin, p-AKT and p-GSK3β did not show significant differences between GES-1 cells that were co-cultured with or without H. pylori. The levels of p-AKT and p-GSK3β were increased in H. pylori-infected Mongolian gerbils. In conclusion, the present study demonstrated that H. pylori infection activated AKT and resulted in the phosphorylation and inactivation of GSK3β, which in turn promoted early stage EMT. These effects were AKT-dependent. This mechanism may serve as a prerequisite for GC development. 相似文献
46.
Melatonin induces apoptosis of colorectal cancer cells through HDAC4 nuclear import mediated by CaMKII inactivation 下载免费PDF全文
Melatonin induces apoptosis in many different cancer cell lines, including colorectal cancer. However, the precise mechanisms involved remain largely unresolved. In this study, we provide evidence to reveal a new mechanism by which melatonin induces apoptosis of colorectal cancer LoVo cells. Melatonin at pharmacological concentrations significantly suppressed cell proliferation and induced apoptosis in a dose‐dependent manner. The observed apoptosis was accompanied by the melatonin‐induced dephosphorylation and nuclear import of histone deacetylase 4 (HDAC4). Pretreatment with a HDAC4‐specific siRNA effectively attenuated the melatonin‐induced apoptosis, indicating that nuclear localization of HDAC4 is required for melatonin‐induced apoptosis. Moreover, constitutively active Ca2+/calmodulin‐dependent protein kinase II alpha (CaMKIIα) abrogated the melatonin‐induced HDAC4 nuclear import and apoptosis of LoVo cells. Furthermore, melatonin decreased H3 acetylation on bcl‐2 promoter, leading to a reduction of bcl‐2 expression, whereas constitutively active CaMKIIα(T286D) or HDAC4‐specific siRNA abrogated the effect of melatonin. In conclusion, the present study provides evidence that melatonin‐induced apoptosis in colorectal cancer LoVo cells largely depends on the nuclear import of HDAC4 and subsequent H3 deacetylation via the inactivation of CaMKIIα. 相似文献
47.
48.
Feng He Yuanjun Ma Shi Li Haozhe Ren Qian Liu Xiaohua Chen Hui Miao Tao Ye Qian Lu Zuge Yang Tianle Li Xin Tong Hongxu Yang Mian Zhang Helin Wang Yazhou Wang Shibin Yu 《Journal of bone and mineral research》2022,37(5):1044-1055
Temporomandibular joint osteoarthritis (TMJOA) is a chronic degenerative disease for which the underlying mechanism still remains unclear. Compared with apoptosis and autophagy, necroptosis causes greater harm to tissue homeostasis by releasing damage-associated molecular patterns (DAMPs). However, the role of necroptosis and downstream key DAMPs in TMJOA is unknown. Here, rodent models of TMJOA were established by the unilateral anterior crossbite (UAC). Transmission electron microscopy (TEM) and immunohistochemistry of receptor interacting protein kinase 3 (RIPK3)/phosphorylation of mixed lineage kinase domain-like protein (pMLKL) were conducted to evaluate the occurrence of necroptosis in vivo. The therapeutic effects of blocking necroptosis were achieved by intra-articularly injecting RIPK3 or MLKL inhibitors and using RIPK3 or MLKL knockout mice. In vitro necroptosis of condylar chondrocyte was induced by combination of tumor necrosis factor alpha (TNFα), second mitochondria-derived activator of caspases (SMAC) mimetics and carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]- fluoromethylketone (z-VAD-fmk). The possible DAMPs released by necroptotic chondrocytes were screened by quantitative proteomics and blocked by specific antibody. Translucent cytosol, swollen organelles, and ruptured cell membranes, features of necroptosis, were frequently manifested in chondrocytes at the early stage of condylar cartilage degeneration in TMJOA, which was accompanied by upregulation of RIPK3/pMLKL. Inhibiting or knocking out RIPK3/MLKL significantly prevented cartilage degeneration. DAMPs released by necroptotic condylar chondrocytes, such as syndecan 4 (SDC4) and heat shock protein 90 (HSP90), were verified. Furthermore, blocking the function of SDC4 significantly attenuated the expression of TNFα in cartilage and synovium, and accordingly increased cartilage thickness and reduced synovial inflammation. Thus, the necroptotic vicious cycle of TNFα-SDC4-TNFα contributes to cartilage degeneration and synovitis, and can serve as a potential therapeutic target for treating TMJOA. © 2022 American Society for Bone and Mineral Research (ASBMR). 相似文献
49.
50.