全文获取类型
收费全文 | 74367篇 |
免费 | 18651篇 |
国内免费 | 4201篇 |
专业分类
97219篇 |
出版年
2024年 | 130篇 |
2023年 | 650篇 |
2022年 | 1580篇 |
2021年 | 2823篇 |
2020年 | 3688篇 |
2019年 | 5547篇 |
2018年 | 5578篇 |
2017年 | 5345篇 |
2016年 | 5993篇 |
2015年 | 6899篇 |
2014年 | 7100篇 |
2013年 | 7716篇 |
2012年 | 6216篇 |
2011年 | 5463篇 |
2010年 | 5439篇 |
2009年 | 3976篇 |
2008年 | 3354篇 |
2007年 | 2617篇 |
2006年 | 2264篇 |
2005年 | 2073篇 |
2004年 | 1789篇 |
2003年 | 1679篇 |
2002年 | 1460篇 |
2001年 | 1241篇 |
2000年 | 985篇 |
1999年 | 881篇 |
1998年 | 509篇 |
1997年 | 445篇 |
1996年 | 442篇 |
1995年 | 369篇 |
1994年 | 361篇 |
1993年 | 262篇 |
1992年 | 341篇 |
1991年 | 297篇 |
1990年 | 230篇 |
1989年 | 183篇 |
1988年 | 155篇 |
1987年 | 173篇 |
1986年 | 132篇 |
1985年 | 128篇 |
1984年 | 88篇 |
1983年 | 68篇 |
1982年 | 67篇 |
1981年 | 48篇 |
1980年 | 37篇 |
1979年 | 44篇 |
1977年 | 32篇 |
1975年 | 29篇 |
1974年 | 34篇 |
1972年 | 33篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
941.
Juan Zhang Zhi-Lin Luan Xiao-Kui Huo Min Zhang Christophe Morisseau Cheng-Peng Sun Bruce D. Hammock Xiao-Chi Ma 《International journal of biological sciences》2023,19(1):294
Acute kidney injury (AKI) is a pathological condition characterized by a rapid decrease in glomerular filtration rate and nitrogenous waste accumulation during hemodynamic regulation. Alisol B, from Alisma orientale, displays anti-tumor, anti-complement, and anti-inflammatory effects. However, its effect and action mechanism on AKI is still unclear. Herein, alisol B significantly attenuated cisplatin (Cis)-induced renal tubular apoptosis through decreasing expressions levels of cleaved-caspase 3 and cleaved-PARP and the ratio of Bax/Bcl-2 depended on the p53 pathway. Alisol B also alleviated Cis-induced inflammatory response (e.g. the increase of ICAM-1, MCP-1, COX-2, iNOS, IL-6, and TNF-α) and oxidative stress (e.g. the decrease of SOD and GSH, the decrease of HO-1, GCLC, GCLM, and NQO-1) through the NF-κB and Nrf2 pathways. In a target fishing experiment, alisol B bound to soluble epoxide hydrolase (sEH) as a direct cellular target through the hydrogen bond with Gln384, which was further supported by inhibition kinetics and surface plasmon resonance (equilibrium dissociation constant, KD = 1.32 μM). Notably, alisol B enhanced levels of epoxyeicosatrienoic acids and decreased levels of dihydroxyeicosatrienoic acids, indicating that alisol B reduced the sEH activity in vivo. In addition, sEH genetic deletion alleviated Cis-induced AKI and abolished the protective effect of alisol B in Cis-induced AKI as well. These findings indicated that alisol B targeted sEH to alleviate Cis-induced AKI via GSK3β-mediated p53, NF-κB, and Nrf2 signaling pathways and could be used as a potential therapeutic agent in the treatment of AKI. 相似文献
942.
Yu'e Liu Yihong Sun Yadong Guo Xiaoyun Shi Xi Chen Wenfeng Feng Lei-Lei Wu Jin Zhang Shibo Yu Yi Wang Yufeng Shi 《International journal of biological sciences》2023,19(3):897
Mitochondria are intracellular organelles involved in energy production, cell metabolism and cell signaling. They are essential not only in the process of ATP synthesis, lipid metabolism and nucleic acid metabolism, but also in tumor development and metastasis. Mutations in mtDNA are commonly found in cancer cells to promote the rewiring of bioenergetics and biosynthesis, various metabolites especially oncometabolites in mitochondria regulate tumor metabolism and progression. And mutation of enzymes in the TCA cycle leads to the unusual accumulation of certain metabolites and oncometabolites. Mitochondria have been demonstrated as the target for cancer treatment. Cancer cells rely on two main energy resources: oxidative phosphorylation (OXPHOS) and glycolysis. By manipulating OXPHOS genes or adjusting the metabolites production in mitochondria, tumor growth can be restrained. For example, enhanced complex I activity increases NAD+/NADH to prevent metastasis and progression of cancers. In this review, we discussed mitochondrial function in cancer cell metabolism and specially explored the unique role of mitochondria in cancer stem cells and the tumor microenvironment. Targeting the OXPHOS pathway and mitochondria-related metabolism emerging as a potential therapeutic strategy for various cancers. 相似文献
943.
Bing-xin Sun Ai-shi Peng Pei-jie Liu Min-jia Wang Hai-li Ding Yu-shi Hu Liang Kang 《Purinergic signalling》2023,19(1):297
The neurotrophin brain-derived neurotrophic factor (BDNF), which acts as a transducer, is responsible for improving cerebral stroke, neuropathic pain, and depression. Exercise can alter extracellular nucleotide levels and purinergic receptors in central nervous system (CNS) structures. This inevitably activates or inhibits the expression of BDNF via purinergic receptors, particularly the P2X receptor (P2XR), to alleviate pathological progression. In addition, the significant involvement of sensitive P2X4R in mediating increased BDNF and p38-MAPK for intracerebral hemorrhage and pain hypersensitivity has been reported. Moreover, archetypal P2X7R blockade induces mouse antidepressant-like behavior and analgesia by BDNF release. This review summarizes BDNF-mediated neural effects via purinergic receptors, speculates that P2X4R and P2X7R could be priming molecules in exercise-mediated changes in BDNF, and provides strategies for the protective mechanism of exercise in neurogenic disease. 相似文献
944.
Ran Wang Zhikang Chen Yi Zhang Shihan Xiao Wuming Zhang Xianqin Hu Qun Xiao Qing Liu Xiangyu Wang 《Journal of cellular and molecular medicine》2023,27(3):392
Flotillin‐1(FLOT1) has long been recognized as a tumour‐promoting gene in several types of cancer. However, the expression and function of FLOT1 in glioblastomas (GBM) has not been elucidated. Here, in this study, we find that the expression level of FLOT1 in GBM tissue was much higher than that in normal brain, and the expression was even higher in the more aggressive subtypes and IDH status of glioma. Kaplan–Meier survival revealed that high FLOT1 expression is closely associated with poor outcome in GBM patients. FLOT1 knockdown markedly reduced the proliferation, migration and invasiveness of GBM cells, while FLOT1 overexpression significantly increases GBM cell proliferation, migration and invasiveness. Mechanistically, FLOT1 expression may play a potential role in the microenvironment of GBM. Therefore, FLOT1 promotes GBM proliferation and invasion in vitro and in vivo and may serve as a biomarker of prognosis and therapeutic potential in the fight against GBM. 相似文献
945.
Yihao Yang Ziyan Shen Youguang Li Chenda Xu Han Xia Hao Zhuang Shengyuan Sun Min Guo Changjie Yan 《植物学报(英文版)》2022,64(10):1860-1865
Rice eating and cooking quality(ECQ) is a major concern of breeders and consumers, determining market competitiveness worldwide. Rice grain protein content(GPC) is negatively related to ECQ,making it possible to improve ECQ by manipulating GPC. However, GPC is genetically complex and sensitive to environmental conditions; therefore, little progress has been made in traditional breeding for ECQ. Here, we report that CRISPR/Cas9-mediated knockout of genes encoding the grain storage protein gluteli... 相似文献
946.
Yi‐Zhe Zhang Juncheng Lin Zhizhong Ren Chun‐Xiang Chen Daisuke Miki Si‐Si Xie Jian Zhang Ya‐Nan Chang Jing Jiang Jun Yan Qingshun Q. Li Jian‐Kang Zhu Cheng‐Guo Duan 《植物学报(英文版)》2021,63(4):707-722
Heterochromatin is widespread in eukaryotic genomes and has diverse impacts depending on its genomic context. Previous studies have shown that a protein complex, the ASI1‐AIPP1‐EDM2 (AAE) complex, participates in polyadenylation regulation of several intronic heterochromatin‐containing genes. However, the genome‐wide functions of AAE are still unknown. Here, we show that the ASI1 and EDM2 mostly target the common genomic regions on a genome‐wide level and preferentially interacts with genetic heterochromatin. Polyadenylation (poly(A) sequencing reveals that AAE complex has a substantial influence on poly(A) site usage of heterochromatin‐containing genes, including not only intronic heterochromatin‐containing genes but also the genes showing overlap with heterochromatin. Intriguingly, AAE is also involved in the alternative splicing regulation of a number of heterochromatin‐overlapping genes, such as the disease resistance gene RPP4. We provided evidence that genic heterochromatin is indispensable for the recruitment of AAE in polyadenylation and splicing regulation. In addition to conferring RNA processing regulation at genic heterochromatin‐containing genes, AAE also targets some transposable elements (TEs) outside of genes (including TEs sandwiched by genes and island TEs) for epigenetic silencing. Our results reveal new functions of AAE in RNA processing and epigenetic silencing, and thus represent important advances in epigenetic regulation. 相似文献
947.
948.
Hong-Guang Zhang Bin Wang Yong Yang Xuan Liu Junjie Wang Ning Xin Shifeng Li Ying Miao Qiuyu Wu Tingting Guo Yukang Yuan Yibo Zuo Xiangjie Chen Tengfei Ren Chunsheng Dong Jun Wang Hang Ruan Miao Sun Xingshun Xu Hui Zheng 《Cell research》2022,32(10):897
Depression is a serious public-health issue. Recent reports have suggested higher susceptibility to viral infections in depressive patients. However, how depression affects antiviral innate immune signaling remains unknown. Here, we revealed a reduction in expression of Abelson helper integration site 1 (AHI1) in the peripheral blood mononuclear cells (PBMCs) and macrophages from the patients with major depressive disorder (MDD), which leads to attenuated antiviral immune response. We found that depression-related arginine vasopressin (AVP) induces reduction of AHI1 in macrophages. Further studies demonstrated that AHI1 is a critical stabilizer of basal type-I-interferon (IFN-I) signaling. Mechanistically, AHI1 recruits OTUD1 to deubiquitinate and stabilize Tyk2, while AHI1 reduction downregulates Tyk2 and IFN-I signaling activity in macrophages from both MDD patients and depression model mice. Interestingly, we identified a clinical analgesic meptazinol that effectively stimulates AHI1 expression, thus enhancing IFN-I antiviral defense in depression model mice. Our study promotes the understanding of the signaling mechanisms of depression-mediated antiviral immune dysfunction, and reveals meptazinol as an enhancer of antiviral innate immunity in depressive patients.Subject terms: Innate immunity, Ubiquitylation, Cell signalling 相似文献
949.