全文获取类型
收费全文 | 16129篇 |
免费 | 1423篇 |
国内免费 | 1374篇 |
出版年
2024年 | 48篇 |
2023年 | 247篇 |
2022年 | 503篇 |
2021年 | 824篇 |
2020年 | 659篇 |
2019年 | 742篇 |
2018年 | 726篇 |
2017年 | 533篇 |
2016年 | 715篇 |
2015年 | 1070篇 |
2014年 | 1272篇 |
2013年 | 1291篇 |
2012年 | 1491篇 |
2011年 | 1329篇 |
2010年 | 900篇 |
2009年 | 740篇 |
2008年 | 791篇 |
2007年 | 709篇 |
2006年 | 691篇 |
2005年 | 558篇 |
2004年 | 486篇 |
2003年 | 515篇 |
2002年 | 397篇 |
2001年 | 243篇 |
2000年 | 211篇 |
1999年 | 204篇 |
1998年 | 138篇 |
1997年 | 112篇 |
1996年 | 115篇 |
1995年 | 109篇 |
1994年 | 93篇 |
1993年 | 58篇 |
1992年 | 78篇 |
1991年 | 64篇 |
1990年 | 60篇 |
1989年 | 44篇 |
1988年 | 28篇 |
1987年 | 24篇 |
1986年 | 34篇 |
1985年 | 25篇 |
1984年 | 13篇 |
1983年 | 7篇 |
1982年 | 8篇 |
1981年 | 5篇 |
1980年 | 3篇 |
1979年 | 3篇 |
1976年 | 2篇 |
1970年 | 1篇 |
1962年 | 2篇 |
1950年 | 1篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
811.
812.
XiaoYan Zhou ChangJiang Ying Bin Hu YuSheng Zhang Tian Gan YanDong Zhu Nan Wang AnAn Li YuanJian Song 《Aging cell》2022,21(2)
In this study, we explored the precise mechanisms underlying the receptor for advanced glycation end products (RAGE)‐mediated neuronal loss and behavioral dysfunction induced by hyperglycemia. We used immunoprecipitation (IP) and GST pull‐down assays to assess the interaction between RAGE and mitogen‐activated protein kinase kinase 3 (MKK3). Then, we investigated the effect of specific mutation of RAGE on plasticity at hippocampal synapses and behavioral deficits in db/db mice through electrophysiological recordings, morphological assays, and behavioral tests. We discovered that RAGE binds MKK3 and that this binding is required for assembly of the MEKK3‐MKK3‐p38 signaling module. Mechanistically, we found that activation of p38 mitogen‐activated protein kinase (MAPK)/NF‐κB signaling depends on mediation of the RAGE‐MKK3 interaction by C‐terminal RAGE (ctRAGE) amino acids (AAs) 2‐5. We found that ctRAGE R2A‐K3A‐R4A‐Q5A mutation suppressed neuronal damage, improved synaptic plasticity, and alleviated behavioral deficits in diabetic mice by disrupting the RAGE‐MKK3 conjugation. High glucose induces direct binding of RAGE and MKK3 via ctRAGE AAs 2‐5, which leads to assembly of the MEKK3‐MKK3‐p38 signaling module and subsequent activation of the p38MAPK/NF‐κB pathway, and ultimately results in diabetic encephalopathy (DE). 相似文献
813.
814.
Yunqing Gu Jun Cao Xinyu Zhang Hai Gao Yuyan Wang Jia Wang Juan He Xiaoyi Jiang Jinlan Zhang Guanghui Shen Jie Yang Xichen Zheng Gaowei Hu Yuanfei Zhu Shujuan Du Yunkai Zhu Rong Zhang Jianqing Xu Fei Lan Di Qu Guoliang Xu Yun Zhao Dong Gao Youhua Xie Min Luo Zhigang Lu 《Cell research》2022,32(1):24-37
Host cellular receptors play key roles in the determination of virus tropism and pathogenesis.However,little is known about SARS-CoV-2 host receptors with the e... 相似文献
815.
Feng Shi Xiaoxia Pang Guangjing Li Zhihong Chen Mingyou Dong Junli Wang 《Journal of cellular and molecular medicine》2022,26(9):2658
The aim of this study was to investigate the effects of forkhead box protein P3 (FOXP3) intron single nucleotide variants (SNVs) in high‐risk human papilloma virus (HR‐HPV) infection and cervical cancer (CC) malignant lesions. We performed FOXP3 genotyping in 350 patients with CC and 350 healthy controls using the ImLDR multiple single nucleotide polymorphism genotyping technology. The heterozygous mutation TC in rs2294021 decreased the risk of HR‐HPV infection and CC malignant lesions (TC vs. TT: OR = 0.71, 95% CI = 0.51–0.99); the dominant model TC+CC and allele C in rs2294021 decreased the risk of CC malignant lesions (TC+CC vs. TT: OR = 0.69, 95% CI = 0.50–0.95; C vs. T: OR = 0.78, 95% CI = 0.63–0.97). The heterozygous mutation GA, dominant model GA+AA and allele A in rs3761549 also decreased the risk of HR‐HPV infection and CC malignant lesions (GA vs. GG: OR = 0.70, 95% CI = 0.51–0.96; GA+AA vs. GG: OR = 0.69, 95% CI = 0.51–0.94; A vs. G: OR = 0.75, 95% CI = 0.58–0.96). Patients with CC and HR‐HPV infection carrying rs2294021 TC and rs3761549 GA had lower expression of FOXP3 protein. Haplotype analysis revealed that T‐C‐A decreased the risk of HR‐HPV infection. Furthermore, we found a significant association between immune cells infiltration and prognosis in patients with CC. Our findings demonstrated that rs2294021 and rs3761549 variants may protect against HR‐HPV and CC malignant lesions by downregulating FOXP3 and that FOXP3 was associated with immune cells infiltration, which affected the prognosis of CC. 相似文献
816.
817.
818.
Manman Zhang Wenliang Gong Dianjun Zhang Ming Ji Binjie Chen Beina Chen Xinyu Li Yuefei Zhou Chengyi Dong Gehua Wen Xiaoni Zhan Xiafang Wu Lulu Cui Yuliang Feng Siman Wang Huiya Yuan Enyu Xu Maosheng Xia Alexei Verkhratsky Baoman Li 《Cell death & disease》2022,13(4)
Alzheimer’s disease (AD) is the prevalent cause of dementia in the ageing world population. Apolipoprotein E4 (ApoE4) allele is the key genetic risk factor for AD, although the mechanisms linking ApoE4 with neurocognitive impairments and aberrant metabolism remains to be fully characterised. We discovered a significant increase in the ApoE4 content of serum exosomes in old healthy subjects and AD patients carrying ApoE4 allele as compared with healthy adults. Elevated exosomal ApoE4 demonstrated significant inverse correlation with serum level of thyroid hormones and cognitive function. We analysed effects of ApoE4-containing peripheral exosomes on neural cells and neurological outputs in aged or thyroidectomised young mice. Ageing-associated hypothyroidism as well as acute thyroidectomy augmented transport of liver-derived ApoE4 reach exosomes into the brain, where ApoE4 activated nucleotide-binding oligomerisation domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome by increasing cholesterol level in neural cells. This, in turn, affected cognition, locomotion and mood. Our study reveals pathological potential of exosomes-mediated relocation of ApoE4 from the periphery to the brain, this process can represent potential therapeutic target.Subject terms: Cognitive neuroscience, Alzheimer''s disease, Cellular neuroscience 相似文献
819.
Jong Taik Moon Sung Hoon Ha So Hyung Lee Tae Hui Kwon Chun Rim Oh Young Deuk Kim Jungahn Kim Dong Joon Choo Jae Yeol Lee 《Bioorganic & medicinal chemistry letters》2010,20(1):52-55
First total synthesis of methylgerambullone (MGB, 1) isolated from Glycosmis angustifolia was completed via a convergent route. The effect of MGB on the contractile responses of the isolated guinea-pig ileum induced by acetylcholine was investigated. As a result, it showed a potent relaxation rate (78.66 ± 4.30% at 100 mg/L) in a concentration-dependent manner on longitudinal smooth muscle contraction of isolated guinea-pig ileum induced by 1 μM acetylcholine. 相似文献
820.