全文获取类型
收费全文 | 21782篇 |
免费 | 1877篇 |
国内免费 | 1375篇 |
出版年
2024年 | 37篇 |
2023年 | 198篇 |
2022年 | 508篇 |
2021年 | 856篇 |
2020年 | 624篇 |
2019年 | 786篇 |
2018年 | 841篇 |
2017年 | 629篇 |
2016年 | 938篇 |
2015年 | 1407篇 |
2014年 | 1634篇 |
2013年 | 1711篇 |
2012年 | 2026篇 |
2011年 | 1936篇 |
2010年 | 1153篇 |
2009年 | 1092篇 |
2008年 | 1259篇 |
2007年 | 1149篇 |
2006年 | 1045篇 |
2005年 | 884篇 |
2004年 | 861篇 |
2003年 | 690篇 |
2002年 | 549篇 |
2001年 | 365篇 |
2000年 | 293篇 |
1999年 | 259篇 |
1998年 | 194篇 |
1997年 | 152篇 |
1996年 | 150篇 |
1995年 | 117篇 |
1994年 | 109篇 |
1993年 | 63篇 |
1992年 | 88篇 |
1991年 | 70篇 |
1990年 | 80篇 |
1989年 | 62篇 |
1988年 | 44篇 |
1987年 | 45篇 |
1986年 | 27篇 |
1985年 | 27篇 |
1984年 | 33篇 |
1983年 | 13篇 |
1982年 | 10篇 |
1981年 | 7篇 |
1980年 | 2篇 |
1978年 | 2篇 |
1967年 | 2篇 |
1965年 | 1篇 |
1964年 | 1篇 |
1962年 | 1篇 |
排序方式: 共有10000条查询结果,搜索用时 250 毫秒
971.
972.
Ying Zhang Jun Wei Jiani Cao Kehua Zhang Yaojin Peng Hongkui Deng Jiuhong Kang Guangjin Pan Yong Zhang Boqiang Fu Shijun Hu Jie Na Yan Liu Lei Wang Lingmin Liang Huanxin Zhu Yu Zhang ZiBing Jin Jie Hao Aijin Ma Tongbiao Zhao Junying Yu 《Cell proliferation》2022,55(4)
‘Requirements for Human‐Induced Pluripotent Stem Cells’ is the first set of guidelines on human‐induced pluripotent stem cells in China, jointly drafted and agreed upon by experts from the Chinese Society for Stem Cell Research. This standard specifies the technical requirements, test methods, and instructions for use, labeling, packaging, storage, transportation, and waste handling for human‐induced pluripotent stem cells, which apply to the production and quality control of human‐induced pluripotent stem cells. It was released by the Chinese Society for Cell Biology on 9 January 2021 and came into effect on 9 April 2021. We hope that the publication of these guidelines will promote institutional establishment, acceptance, and execution of proper protocols and accelerate the international standardization of human‐induced pluripotent stem cells for applications. 相似文献
973.
974.
975.
Wentao Liu Bin Yan Haixin Yu Jiannan Ren Mou Peng Liang Zhu Yinhuai Wang Xin Jin Lu Yi 《International journal of biological sciences》2022,18(4):1401
Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cell carcinoma and has the highest mortality rate. For metastatic RCC, systemic drug therapy is the most important method in addition to surgical tumor reduction. In recent years, tyrosine kinase inhibitors (TKIs) targeting the angiogenesis have been applied to treat ccRCC and achieved profound therapeutic effects. It has been reported that most patients receiving antiangiogenic therapy will develop resistance within 15 months. The mechanism of resistance to targeted therapy is extremely complex and has not been clarified. Ovarian tumor-associated protease domain-containing proteins (OTUDs) belonging to DUBs play a critical role in the tumorigenesis of solid tumors. However, the specific role of OTUDs in ccRCC is still elusive. Here, we investigated the clinicopathological role of OTUD family members in ccRCC. We demonstrated that OTUD1 was downregulated in renal cancer and involved in the poor prognosis of renal cancer. Then, we showed that OTUD1 inhibits cancer cell growth. Moreover, analysis of OTUD1 RNA-seq data indicated that OTUD1 inhibition triggers the AKT and NF-kappa B pathways in renal cancer cells. Furthermore, OTUD1 interacts with PTEN and regulates its stability. Subsequently, we revealed that downregulation of OTUD1 contributes to the sensitivity of renal cancer cells to TKIs, and this effect was blocked by TNF/NF-kappa B inhibitors and AKT inhibitors. Thus, we identified that the OTUD1-PTEN axis suppresses tumor growth and regulates the resistance of renal cancer to TKIs. 相似文献
976.
Jin Zhao Jiaoshan Chen Congcong Wang Yajie Liu Minchao Li Yanjun Li Ruiting Li Zirong Han Junjian Wang Ling Chen Yuelong Shu Genhong Cheng Caijun Sun 《PLoS pathogens》2022,18(3)
Tryptophan (Trp) metabolism through the kynurenine pathway (KP) is well known to play a critical function in cancer, autoimmune and neurodegenerative diseases. However, its role in host-pathogen interactions has not been characterized yet. Herein, we identified that kynurenine-3-monooxygenase (KMO), a key rate-limiting enzyme in the KP, and quinolinic acid (QUIN), a key enzymatic product of KMO enzyme, exerted a novel antiviral function against a broad range of viruses. Mechanistically, QUIN induced the production of type I interferon (IFN-I) via activating the N-methyl-d-aspartate receptor (NMDAR) and Ca2+ influx to activate Calcium/calmodulin-dependent protein kinase II (CaMKII)/interferon regulatory factor 3 (IRF3). Importantly, QUIN treatment effectively inhibited viral infections and alleviated disease progression in mice. Furthermore, kmo-/- mice were vulnerable to pathogenic viral challenge with severe clinical symptoms. Collectively, our results demonstrated that KMO and its enzymatic product QUIN were potential therapeutics against emerging pathogenic viruses. 相似文献
977.
Ji-Cheng Huang Cui-Cui Duan Shan Jin Chuan-Bo Sheng Yu-Si Wang Zhan-Peng Yue Bin Guo 《International journal of biological sciences》2022,18(5):2047
Polycystic ovarian syndrome (PCOS) is one of the most prevalent endocrinopathies and the leading cause of anovulatory infertility, but its pathogenesis remains elusive. Although HB-EGF is involved in ovarian cancer progression, there is still no clarity about its relevance with PCOS. The present study exhibited that abundant HB-EGF was noted in follicular fluid from PCOS women, where it might induce the granulosa cells (GCs) production of more estrogen via the elevation of CYP19A1 expression after binding to EGFR. Furthermore, HB-EGF transduced intracellular downstream cAMP-PKA signaling to promote the phosphorylation of JNK and ERK whose blockage impeded the induction of HB-EGF on estrogen secretion. Meanwhile, HB-EGF enhanced the accumulation of intracellular Ca2+ whose chelation by BAPTA-AM abrogated the stimulation of HB-EGF on FOXO1 along with an obvious diminishment for estrogen production. cAMP-PKA-JNK/ERK-Ca2+ pathway played an important role in the crosstalk between HB-EGF and FOXO1. Treatment of GCs with HB-EGF resulted in mitochondrial dysfunction as evinced by the reduction of ATP content, mtDNA copy number and mitochondrial membrane potential. Additionally, HB-EGF facilitated the opening of mitochondrial permeability transition pore via targeting BAX and raised the release of cytochrome C from mitochondria into the cytosol to trigger the apoptosis of GCs, but this effectiveness was counteracted by estrogen receptor antagonist. Collectively, HB-EGF might induce mitochondrial dysfunction and GCs apoptosis through advancing estrogen hypersecretion dependent on cAMP-PKA-JNK/ERK-Ca2+-FOXO1 pathway and act as a promising therapeutic target for PCOS. 相似文献
978.
为研究当前主动型下肢假肢控制问题的解决策略,提出了主动型下肢假肢设计和分类的通用控制框架,包括3个分层结构:上层控制器、中层控制器、底层控制器。其中,上层控制器感知运动意图;中层控制器将运动意图转换为预期的装置状态,用于底层控制器的跟踪参考;底层控制器通过反馈控制或者前馈控制计算出预期装置状态与当前装置状态的误差,驱动假肢执行这些命令,形成控制闭环。结果表明,该通用控制框架可完整阐释主动型下肢假肢的人—机—环境共融关系,明确了分层控制策略的层级任务,为未来主动型下肢假肢的发展提供了理论指导。 相似文献
979.
980.
Biao Wang Xueyi Li Ming Li Yan Geng Na Wang Yaofeng Jin Wen Zhang Ke Xu Jing Wang Li Tao Simin Lai Kunyi Wu Jing Lei Jing Wang Ting Zhou Ke Li Yanjiong Chen Li Xue 《Cell death & disease》2022,13(3)
Dopamine receptors are involved in several immunological diseases. We previously found that dopamine D3 receptor (D3R) on mast cells showed a high correlation with disease activity in patients with rheumatoid arthritis, but the mechanism remains largely elusive. In this study, a murine collagen-induced arthritis (CIA) model was employed in both DBA/1 mice and D3R knockout mice. Here, we revealed that D3R-deficient mice developed more severe arthritis than wild-type mice. D3R suppressed mast cell activation in vivo and in vitro via a Toll-like receptor 4 (TLR4)-dependent pathway. Importantly, D3R promoted LC3 conversion to accelerate ubiquitin-labeled TLR4 degradation. Mechanistically, D3R inhibited mTOR and AKT phosphorylation while enhancing AMPK phosphorylation in activated mast cells, which was followed by autophagy-dependent protein degradation of TLR4. In total, we found that D3R on mast cells alleviated inflammation in mouse rheumatoid arthritis through the mTOR/AKT/AMPK-LC3-ubiquitin-TLR4 signaling axis. These findings identify a protective function of D3R against excessive inflammation in mast cells, expanding significant insight into the pathogenesis of rheumatoid arthritis and providing a possible target for future treatment.Subject terms: Immunological disorders, Rheumatic diseases 相似文献