全文获取类型
收费全文 | 339810篇 |
免费 | 29964篇 |
国内免费 | 12073篇 |
专业分类
耳鼻咽喉 | 2230篇 |
儿科学 | 7459篇 |
妇产科学 | 4090篇 |
基础医学 | 58384篇 |
口腔科学 | 6676篇 |
临床医学 | 27515篇 |
内科学 | 52007篇 |
皮肤病学 | 4583篇 |
神经病学 | 22735篇 |
特种医学 | 8075篇 |
外国民族医学 | 78篇 |
外科学 | 26393篇 |
综合类 | 47430篇 |
现状与发展 | 40篇 |
一般理论 | 25篇 |
预防医学 | 19336篇 |
眼科学 | 6324篇 |
药学 | 40242篇 |
34篇 | |
中国医学 | 14067篇 |
肿瘤学 | 34124篇 |
出版年
2024年 | 753篇 |
2023年 | 4610篇 |
2022年 | 9623篇 |
2021年 | 12627篇 |
2020年 | 10890篇 |
2019年 | 12254篇 |
2018年 | 11806篇 |
2017年 | 11611篇 |
2016年 | 11649篇 |
2015年 | 13025篇 |
2014年 | 18923篇 |
2013年 | 21353篇 |
2012年 | 18840篇 |
2011年 | 22131篇 |
2010年 | 18976篇 |
2009年 | 18282篇 |
2008年 | 17737篇 |
2007年 | 17679篇 |
2006年 | 16157篇 |
2005年 | 14748篇 |
2004年 | 12833篇 |
2003年 | 11597篇 |
2002年 | 9008篇 |
2001年 | 8344篇 |
2000年 | 6736篇 |
1999年 | 6154篇 |
1998年 | 4759篇 |
1997年 | 4310篇 |
1996年 | 4017篇 |
1995年 | 3593篇 |
1994年 | 3150篇 |
1993年 | 2758篇 |
1992年 | 2366篇 |
1991年 | 2074篇 |
1990年 | 1727篇 |
1989年 | 1557篇 |
1988年 | 1416篇 |
1987年 | 1104篇 |
1986年 | 944篇 |
1985年 | 1403篇 |
1984年 | 1444篇 |
1983年 | 984篇 |
1982年 | 1140篇 |
1981年 | 940篇 |
1980年 | 793篇 |
1979年 | 666篇 |
1978年 | 527篇 |
1977年 | 415篇 |
1976年 | 429篇 |
1975年 | 289篇 |
排序方式: 共有10000条查询结果,搜索用时 0 毫秒
101.
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
102.
《Clinical Lymphoma, Myeloma & Leukemia》2020,20(8):e461-e467
IntroductionVon Willebrand factor (vWF) cleaving protease ADAMTS-13 has a key role for maintaining normal size of vWF. A deficiency or dysfunction of vWF cleaving protease is associated with ultra large vWF multimers and thrombotic microangiopathy. Patients with cancers have reduced levels of vWF cleaving protease. In this pilot study, we have evaluated whether or not deficiencies of ADAMTS-13 were present in myelodysplastic syndromes (MDS). Moreover, we assessed if a reduction in basal levels of ADAMTS-13 may play a role in the prognosis of MDS.Patients and MethodsWe measured and compared the levels of vWF cleaving protease ADAMTS-13 in 100 patients with MDS and 35 healthy controls. Patients were divided into 2 groups according to the International Prognostic Scoring System: group I consisting of 44 patients with low-risk MDS and group II of 56 patients with high-risk MDS. Patients with high-risk and low-risk MDS presented significantly lower levels of ADAMTS-13 than controls (P < .001 and P = .0177, respectively). High-risk patients had significantly lower levels of ADAMTS-13 when compared with the low-risk group (P < .001).ResultsWe found that reduced levels of ADAMTS-13 have a relationship with overall survival (P < .001). Statistical analysis showed that ADAMTS-13 correlates with cytogenetics (P < .001) and a tendency of slight correlation with platelet count and basal levels of ADAMTS-13 (R, 0.35; P value, 0.001). Moreover, we found that levels of ADAMTS-13 have correlation with response to treatment (P < .001).ConclusionsADAMTS-13 in MDS might represent a surrogate marker of prognosis, response to therapy, or disease progression. Further studies are needed. 相似文献
103.
104.
随着对肿瘤热疗和肿瘤免疫微环境(TIME)的深入研究,近年来热疗对TIME的作用越来越受到学者们的重视。本文就目前国内外研究进展,对热疗与TIME中几类主要免疫细胞和免疫相关细胞因子的影响及作用机制作一综述。全面而透彻的了解热疗对TIME的调控作用,有助于为肿瘤治疗提供新的思路和方法。 相似文献
105.
- Download : Download high-res image (66KB)
- Download : Download full-size image
106.
Melatonin induces apoptosis of colorectal cancer cells through HDAC4 nuclear import mediated by CaMKII inactivation
下载免费PDF全文
![点击此处可从《Journal of pineal research》网站下载免费的PDF全文](/ch/ext_images/free.gif)
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
107.
108.
109.
Michelle Linda Ferderbar Thomas E. Doyle Reza Samavi David Koff 《Journal l'Association canadienne des radiologistes》2019,70(2):119-124
Several regulatory bodies have agreed that low-dose radiation used in medical imaging is a weak carcinogen that follows a linear, non-threshold model of cancer risk. While avoiding radiation is the best course of action to mitigate risk, computed tomography (CT) scans are often critical for diagnosis. In addition to the as low as reasonably achievable principle, a more concrete method of dose reduction for common CT imaging exams is the use of a diagnostic reference level (DRL). This paper examines Canada's national DRL values from the recent CT survey and compares it to published provincial DRLs as well as the DRLs in the United Kingdom and the United States of America for the 3 most common CT exams: head, chest, and abdomen/pelvis. Canada compares well on the international scale, but it should consider using more electronic dose monitoring solutions to create a culture of dose optimization. 相似文献
110.
Mengdie Jiang Bihan Wu Yongbing Sun Yanhuai Ding Yixi Xie 《Toxicology mechanisms and methods》2019,29(4):291-299
In a biological microenvironment, free fatty acids (FFA) as ubiquitous biological molecules might interact with nanoparticles (NPs) and consequently change the toxicological responses. However, whether the chemical structures of FFA could influence their interactions with NPs remain unknown. This study investigated the interactions between ZnO NPs and saturated or unsaturated FFA (complexed to BSA), namely stearic acid (SA, C18:0), oleic acid (OA, C18:1), and α-linolenic acid (ALA, C18:3). It was shown that BSA, SA, OA, and ALA increased the atomic force microscope (AFM) heights as well the polydispersity index (PDI) of ZnO NPs. BSA modestly protected THP-1 macrophages from ZnO NP exposure, whereas OA and ALA led to relatively less cyto-protective effects of BSA. Moreover, only co-exposure to ZnO NPs and SA significantly promoted the release of interleukin-8. BSA, SA, OA, and ALA equally changed intracellular ROS and Zn ions associated with ZnO exposure, but co-exposure to ZnO NPs and OA/ALA particularly activated the expression of endoplasmic reticulum stress-apoptosis genes. In combination, these results showed that FFA could influence the colloidal aspects and toxicological signaling pathway of ZnO NPs, which is dependent on the number of unsaturated bonds of FFA. 相似文献