全文获取类型
收费全文 | 97021篇 |
免费 | 9557篇 |
国内免费 | 6612篇 |
专业分类
耳鼻咽喉 | 655篇 |
儿科学 | 1197篇 |
妇产科学 | 1365篇 |
基础医学 | 11458篇 |
口腔科学 | 1908篇 |
临床医学 | 12252篇 |
内科学 | 14425篇 |
皮肤病学 | 1045篇 |
神经病学 | 5345篇 |
特种医学 | 3685篇 |
外国民族医学 | 36篇 |
外科学 | 9766篇 |
综合类 | 16492篇 |
现状与发展 | 15篇 |
一般理论 | 13篇 |
预防医学 | 6613篇 |
眼科学 | 2548篇 |
药学 | 10553篇 |
87篇 | |
中国医学 | 5691篇 |
肿瘤学 | 8041篇 |
出版年
2024年 | 258篇 |
2023年 | 1441篇 |
2022年 | 2525篇 |
2021年 | 4717篇 |
2020年 | 3686篇 |
2019年 | 3212篇 |
2018年 | 3396篇 |
2017年 | 3076篇 |
2016年 | 2967篇 |
2015年 | 4436篇 |
2014年 | 5389篇 |
2013年 | 5141篇 |
2012年 | 7576篇 |
2011年 | 8063篇 |
2010年 | 5288篇 |
2009年 | 4262篇 |
2008年 | 5547篇 |
2007年 | 5391篇 |
2006年 | 4806篇 |
2005年 | 4620篇 |
2004年 | 3512篇 |
2003年 | 3324篇 |
2002年 | 3020篇 |
2001年 | 2409篇 |
2000年 | 2352篇 |
1999年 | 2322篇 |
1998年 | 1468篇 |
1997年 | 1422篇 |
1996年 | 1128篇 |
1995年 | 1061篇 |
1994年 | 870篇 |
1993年 | 554篇 |
1992年 | 629篇 |
1991年 | 579篇 |
1990年 | 497篇 |
1989年 | 433篇 |
1988年 | 346篇 |
1987年 | 339篇 |
1986年 | 263篇 |
1985年 | 205篇 |
1984年 | 138篇 |
1983年 | 90篇 |
1982年 | 67篇 |
1981年 | 48篇 |
1980年 | 34篇 |
1979年 | 50篇 |
1978年 | 18篇 |
1973年 | 17篇 |
1972年 | 17篇 |
1966年 | 18篇 |
排序方式: 共有10000条查询结果,搜索用时 203 毫秒
61.
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
62.
63.
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
64.
65.
66.
67.
目的 探讨接受新辅助放化疗的局部晚期食管鳞癌患者新辅助放疗剂量与病理完全缓解(pCR)的关系。方法 收集2017-2019年间在四川大学华西医院肿瘤中心经病理确诊为食管鳞癌并接受新辅助放化疗和手术的 116例局部晚期患者临床资料。116例患者中 40~45Gy组 80例,≥45Gy组 36例,分析两组术后pCR率。结果 全组患者的pCR率为38.8%(45/116),40~45Gy组与≥45Gy组的pCR率分别为44%(35/80)和28%(10/36)(P=0.105)。结论 术前新辅助采用较高的放疗剂量不增加局部晚期食管鳞癌的pCR率,有必要进行前瞻性的临床研究确定合适的新辅助放疗剂量。 相似文献
68.
Shiyu Jiang Yan Qin Hongxin Jiang Biao Liu Jianming Shi Fanlu Meng Peng Liu Jianliang Yang Sheng Yang Xiaohui He Shengyu Zhou Lin Gui Hao Liu Jing Lin Han Han-Zhang Yuankai Shi 《International journal of cancer. Journal international du cancer》2020,147(9):2611-2620
Diffuse large B-cell lymphoma (DLBCL) is a clinically aggressive and heterogenous disease. Although most patients can be cured by immunochemotherapy, 30% to 40% patient will ultimately develop relapsed or refractory disease. Here, we investigated the molecular landscapes of patients with diverse responses to R-CHOP. We performed capture-based targeted sequencing on baseline samples of 105 DLBCL patients using a panel consisting of 112 lymphoma-related genes. Subsequently, 81 treatment-naïve patients with measurable disease and followed for over 1 year were included for survival analysis. Collectively, the most commonly seen mutations included IGH fusion (69%), PIM1(33%), MYD88 (29%), BCL2 (29%), TP53 (29%), CD79B (25%) and KMT2D (24%). Patients with TP53 mutations were more likely to have primary refractory disease (87.0% vs 50.0%, P = .009). For those with TP53 disruptive mutations, 91.7% patients were in the primary refractory group. Interestingly, BCL-2 somatic hypermutation was only seen in patients without primary refractory disease (P = .014). In multivariate analysis, BCL-2 amplification (hazard ratio [HR] = 2.94, P = .022), B2M mutation (HR = 2.99, P = .017) and TP53 mutation (HR = 3.19, P < .001) were independently associated with shorter time to progression (TTP). Furthermore, TP53 mutations was correlated with worse overall survival (P = .049). Next, we investigated mutation landscape in patients with wild-type (WT) TP53 (n = 58) and found that patients harboring MYD88 L265P had significantly inferior TTP than those with WT or non-265P (P = .046). Our study reveals the mutation spectrum of treatment-naive Chinese DLBCL patients. It also confirms the clinical significance of TP53 mutations and indicates the prognostic value of MYD88 L265P in TP53 WT patients. 相似文献
69.
70.
Peffault de Latour Rgis Huynh Lynn Ivanova Jasmina I. Totev Todor Bilginsoy Mehmet Antin Joseph Roy Anuja Duh Mei Sheng 《Annals of hematology》2020,99(4):743-752
Annals of Hematology - This study assessed treatment patterns and healthcare resource utilization (HRU) of patients with severe aplastic anemia (SAA) with insufficient response to immunosuppressive... 相似文献