全文获取类型
收费全文 | 9267篇 |
免费 | 707篇 |
国内免费 | 989篇 |
专业分类
10963篇 |
出版年
2024年 | 24篇 |
2023年 | 124篇 |
2022年 | 313篇 |
2021年 | 508篇 |
2020年 | 378篇 |
2019年 | 450篇 |
2018年 | 375篇 |
2017年 | 275篇 |
2016年 | 410篇 |
2015年 | 585篇 |
2014年 | 699篇 |
2013年 | 784篇 |
2012年 | 888篇 |
2011年 | 766篇 |
2010年 | 492篇 |
2009年 | 464篇 |
2008年 | 531篇 |
2007年 | 471篇 |
2006年 | 385篇 |
2005年 | 297篇 |
2004年 | 295篇 |
2003年 | 260篇 |
2002年 | 212篇 |
2001年 | 147篇 |
2000年 | 128篇 |
1999年 | 130篇 |
1998年 | 84篇 |
1997年 | 65篇 |
1996年 | 56篇 |
1995年 | 61篇 |
1994年 | 64篇 |
1993年 | 41篇 |
1992年 | 36篇 |
1991年 | 43篇 |
1990年 | 31篇 |
1989年 | 23篇 |
1988年 | 12篇 |
1987年 | 10篇 |
1986年 | 12篇 |
1985年 | 12篇 |
1984年 | 4篇 |
1983年 | 5篇 |
1982年 | 4篇 |
1981年 | 3篇 |
1980年 | 3篇 |
1977年 | 3篇 |
排序方式: 共有10000条查询结果,搜索用时 0 毫秒
51.
Yudan Zhao Yongwu Yang Min Liu Xuening Qin Xiran Yu Huimin Zhao Xiaoyun Li Wei Li 《PLoS neglected tropical diseases》2022,16(4)
Giardia duodenalis, the causative agent of giardiasis, is among the most important causes of waterborne diarrheal diseases around the world. Giardia infection may persist over extended periods with intestinal inflammation, although minimal. Cyclooxygenase (COX)-2 is well known as an important inducer of inflammatory response, while the role it played in noninvasive Giardia infection remains elusive. Here we investigated the regulatory function of COX-2 in Giardia-induced pro-inflammatory response and defense-related nitric oxide (NO) generation in macrophage-like cell line, and identified the potential regulators. We initially found that Giardia challenge induced up-regulation of IL-1β, IL-6, TNF-α, prostaglandin (PG) E2, and COX-2 in macrophages, and pretreatment of the cells with COX-2 inhibitor NS398 reduced expressions of those pro-inflammatory factors. It was also observed that COX-2 inhibition could attenuate the up-regulated NO release and inducible NO synthase (iNOS) expression induced by Giardia. We further confirmed that Giardia-induced COX-2 up-regulation was mediated by the phosphorylation of p38 and ERK1/2 MAPKs and NF-κB. In addition, inhibition of reactive oxygen species (ROS) by NAC was shown to repress Giardia-induced activation of MAPK/NF-κB signaling, up-regulation of COX-2 and iNOS, increased levels of PGE2 and NO release, and up-expressions of IL-1β, IL-6, and TNF-α. Collectively, in this study, we revealed a critical role of COX-2 in modulating pro-inflammatory response and defense-related NO production in Giardia-macrophage interactions, and this process was evident to be controlled by ROS-dependent activation of MAPK/NF-κB signaling. The results can deepen our knowledge of anti-Giardia inflammatory response and host defense mechanisms. 相似文献
52.
Yuting Wen Meng Cheng Lang Qin Wenming Xu 《Journal of cellular and molecular medicine》2022,26(10):2947
Early spontaneous abortion (ESA) is one of the most common complications during pregnancy and the inflammation condition in uterine environment such as long‐term exposure to high TNFα plays an essential role in the aetiology. Ferritin heavy chain (FTH1) is considered to be closely associated with inflammation and very important in normal pregnancy, yet the underlying mechanism of how TNFα induced abortion and its relationship with FTH1 remain elusive. In this study, we found that TNFα and FTH1 were positively expressed in decidual stromal cells and increased significantly in the ESA group compared with the normal pregnancy group (NP group). Besides, TNFα expression was positively correlated with FTH1 expression. Furthermore, in vitro cell model demonstrated that high TNFα could induce the abnormal signals of TNFR/NF‐κB/FTH1 and activate apoptosis both in human endometrium stromal cells (hESCs) and in local decidual tissues. Taken together, the present findings suggest that the excessive apoptosis in response to TNFα‐induced upregulation of FTH1 may be responsible for the occurrence of ESA, and thus provide a possible therapeutic target for the treatment of ESA. 相似文献
53.
54.
Meizhi Xu Xu Gu Nengsong Liang Xinxin Bian Hong Wang Yaxin Qin Limin Pi Shuang Wu 《植物学报(英文版)》2020,62(7):897-911
Root stem cell niche (SCN) consists of a quiescent center (QC) and surrounding stem cells. Disrupted symplastic communication leads to loss of stemness in the whole SCN. Several SCN regulators were reported to move between cells for SCN maintenance. However, single mutant of these regulators is insufficient to abolish QC stemness despite the high differentiation rate in surrounding stem cells. To dissect the mechanism behind such distinct stemness in SCN, we combined the mis‐expression strategy with pWOX5:icals3m system in which QC is symplastically isolated. We found the starch accumulation in QC could be synergistically repressed by WUSCHEL‐RELATED HOMEOBOX 5 (WOX5), SHORT‐ROOT (SHR), SCARCROW (SCR), and PLETHORA (PLT). Like PLTs, other core regulators also exhibited dimorphic functions by inhibiting differentiation at a higher dose while promoting cell division at a low protein level. Being located in the center of the intersected expression zones, QC cells receive the highest level of core regulators, forming the most robust stemness within SCN. WUSCHEL‐RELATED HOMEOBOX 5 was sufficient to activate PLT1/2 expression, contributing to the QC‐enriched PLTs. Our results provide experimental evidence supporting the long‐standing hypothesis that the combination of spatial expression, synergistic function and dosage effect of core regulators result in spatially distinct stemness in SCN. 相似文献
55.
Cancan Du Xixi Duan Xiaohan Yao Jiajia Wan Yanru Cheng Yuan Wang Yan Yan Lijing Zhang Linyu Zhu Chen Ni Ming Wang Zhihai Qin 《Journal of cellular and molecular medicine》2020,24(14):7802-7813
Tumour‐derived exosomes have been shown to induce pre‐metastatic niche formation, favoring metastatic colonization of tumour cells, but the underlying molecular mechanism is still not fully understood. In this study, we showed that exosomes derived from the LLC cells could indeed significantly enhance their intrapulmonary colonization. Circulating LLC‐derived exosomes were mainly engulfed by lung fibroblasts and led to the NF‐κB signalling activation. Further studies indicated that the exosomal miR‐3473b was responsible for that by hindering the NFKB inhibitor delta's (NFKBID) function. Blocking miR‐3473b could reverse the exosome‐mediated NF‐κB activation of fibroblasts and decrease intrapulmonary colonization of lung tumour cells. Together, this study demonstrated that the miR‐3473b in exosomes could mediate the interaction of lung tumour cells and local fibroblasts in metastatic sites and, therefore, enhance the metastasis of lung tumour cells. 相似文献
56.
Xuan Che Jianzhang Wang Jiayi He Qin Yu Wenting Sun Shuyi Chen Gen Zou Tiantian Li Xinyue Guo Xinmei Zhang 《Journal of cellular and molecular medicine》2020,24(2):1724-1737
Adenomyosis is also called internal endometriosis and affects about 20% of reproductive‐aged women. It seriously reduces life quality of patients because current drug therapies face with numerous challenges. Long‐term clinical application of mifepristone exhibits wonderful therapeutic effects with mild side‐effects in many disorders since 1982. Since adenomyosis is a refractory disease, we investigate whether mifepristone can be applied in the treatment of adenomyosis. In this study, we investigated the direct effects of mifepristone on human primary eutopic endometrial epithelial cells and stromal cells in adenomyosis. We found that mifepristone causes cell cycle arrest through inhibiting CDK1 and CDK2 expressions and induces cell apoptosis via the mitochondria‐dependent signalling pathway in endometrial epithelial cells and stromal cells of adenomyosis. Furthermore, mifepristone inhibits the migration of endometrial epithelial cells and stromal cells through decreasing CXCR4 expression and restricts the invasion of endometrial epithelial cells via suppression of epithelial‐mesenchymal transition in adenomyosis. We also found that mifepristone treatment decreases the uterine volume, CA125 concentration and increases the haemoglobin concentration in serum for adenomyosis patients. Therefore, we demonstrate that mifepristone could serve as a novel therapeutic drug in the treatment of adenomyosis, and therefore, the old dog can do a new trick. 相似文献
57.
58.
59.
Science China Life Sciences - 相似文献