全文获取类型
收费全文 | 18728篇 |
免费 | 1628篇 |
国内免费 | 2117篇 |
出版年
2024年 | 51篇 |
2023年 | 295篇 |
2022年 | 663篇 |
2021年 | 1114篇 |
2020年 | 807篇 |
2019年 | 950篇 |
2018年 | 817篇 |
2017年 | 613篇 |
2016年 | 890篇 |
2015年 | 1239篇 |
2014年 | 1516篇 |
2013年 | 1455篇 |
2012年 | 1775篇 |
2011年 | 1528篇 |
2010年 | 963篇 |
2009年 | 824篇 |
2008年 | 1016篇 |
2007年 | 853篇 |
2006年 | 721篇 |
2005年 | 635篇 |
2004年 | 562篇 |
2003年 | 456篇 |
2002年 | 388篇 |
2001年 | 341篇 |
2000年 | 300篇 |
1999年 | 299篇 |
1998年 | 202篇 |
1997年 | 172篇 |
1996年 | 136篇 |
1995年 | 136篇 |
1994年 | 113篇 |
1993年 | 80篇 |
1992年 | 100篇 |
1991年 | 81篇 |
1990年 | 62篇 |
1989年 | 77篇 |
1988年 | 47篇 |
1987年 | 48篇 |
1986年 | 29篇 |
1985年 | 40篇 |
1984年 | 25篇 |
1983年 | 21篇 |
1982年 | 13篇 |
1981年 | 6篇 |
1980年 | 2篇 |
1979年 | 3篇 |
1978年 | 3篇 |
1975年 | 1篇 |
1965年 | 1篇 |
1950年 | 2篇 |
排序方式: 共有10000条查询结果,搜索用时 500 毫秒
981.
Qi Wang Quanwei Zhang Yong Zhang Xingxu Zhao 《Journal of cellular biochemistry》2019,120(4):6729-6740
Oxoglutarate receptor 1 (OXGR1), as one of the intermediates in G protein-coupled receptors (GPCRs), plays a crucial role in the citric acid cycle receptor of α-ketoglutarate and metabolism. GPCR can control the cell proliferation by regulating the downstream signaling of G protein signaling pathways. The PI3K/AKT pathway transmits the downstream signals of GPCRs and receptor tyrosine kinases. However, the specific role of OXGR1 promoting cell proliferation and differentiation are still unknown. In current study, the over-expression vector and knockdown sequence of yak OXGR1 were transfected into yak fibroblasts, and the effects were detected by a series of assays. The results revealed that OXGR1 expression in yak lung parenchyma tissue was significantly higher than that of other tissues. In yak fibroblasts, the upregulated expression of OXGR1 resulted in activating the PIK3CG (downstream signal) of the PI3K/AKT1 pathway that can upregulated the expression of proliferation genes ( CDK1, PCNA, and CyclinD1) and promote cell proliferation. Conversely, the downregulated expression of OXGR1 inhibited cell proliferation via PI3K/AKT1 pathway. Cell cycle and cell proliferation assays demonstrated that over-expression of OXGR1 can enhanced the DNA synthesis and promoted yak fibroblasts proliferation. While the conversely, knockdown of OXGR1 can decreased DNA synthesis and inhibited cell proliferation. These results illustrated that changes of OXGR1 expression can trigger the fibroblasts proliferation via PI3K/AKT signaling pathway, which indicating that OXGR1 is a novel regulator for cell proliferation and differentiation. Furthermore, these results provide evidence supporting the functional role of GPCRs-PI3K-AKT1 and OXGR1 in cell proliferation. 相似文献
982.
983.
984.
985.
986.
Qi Zou MD Chong-Jie Zhang MD Yu-Zhong Yan MD Zhi-Jun Min MD Chun-Sheng Li MD 《Journal of cellular biochemistry》2019,120(11):18650-18658
This study aims to explore the ability of magnetic resonance imaging (MRI) in mucin 1 (MUC1) modified superparamagnetic iron oxide nanoparticle (SPION) targeting human pancreatic cancer (PC). The MUC1 target-directed probe was prepared through MUC1 conjugated to SPION using the chemical method to assess its physiochemical characteristics, including hydration diameter, surface charge, and magnetic resonance signal. The cytotoxicity of MUC1-USPION was verified by MTS assay. BxPC-3 was cultured with MUC1-USPION and SPION in different concentrations. The combined condition of the targeted probes and cells were observed through Prussian blue staining. The nude mice model of pancreatic cancer was established to investigate the application of the probe. MRI was performed to determine the intensity of the signal of the transplanted tumor, while immunohistochemistry and Western blot analysis were performed to detect the expression of MUC1 after taking the transplanted tumor specimen. The particle size of the prepared molecular probe was 63.5 ± 3.2 nm, and the surface charge was 10.2 mV. Furthermore, the probe solution could significantly reduce the MRI at T2, and the magnetic resonance transverse relaxation rate (ΔR2) has a linear relationship with the concentration of iron in the solution. The cell viability of MUC1-USPION in different concentrations revealed no statistical difference, according to the MTS assay. In vitro, the MRI demonstrated decreased T2WI signal intensity in both groups, especially the targeting group. In vivo, MUC1 could selectively accumulate in the nude mice model, and significantly reduce the T2 signal strength. In subsequent experiments, the expression of MUC1 was high in pancreatic cancer tissues, but low in normal pancreatic tissues, as determined by immunohistochemistry and Western blot analysis. The prepared samples can be combined with pancreatic cancer tissue specificity by in vivo imaging, providing reliable early in vivo imaging data for disease diagnosis. 相似文献
987.
988.
989.
Chao Wang Yuelin Li Zi Liu Zeyu Wang Zihan Liu Shuai Man Yujing Zhang Kai Bao Yingliang Wu Qi Guan Daiying Zuo Weige Zhang 《Journal of enzyme inhibition and medicinal chemistry》2021,36(1):549
A series of 1-aryl-5-(4-arylpiperazine-1-carbonyl)-1H-tetrazols as microtubule destabilizers were designed, synthesised and evaluated for anticancer activity. Based on bioisosterism, we introduced the tetrazole moiety containing the hydrogen-bond acceptors as B-ring of XRP44X analogues. The key intermediates ethyl 1-aryl-1H-tetrazole-5-carboxylates 10 can be simply and efficiently prepared via a microwave-assisted continuous operation process. Among the compounds synthesised, compound 6–31 showed noteworthy potency against SGC-7901, A549 and HeLa cell lines. In mechanism studies, compound 6–31 inhibited tubulin polymerisation and disorganised microtubule in SGC-7901 cells by binding to tubulin. Moreover, compound 6–31 arrested SGC-7901cells in G2/M phase. This study provided a new perspective for development of antitumor agents that target tubulin. 相似文献
990.
生长素输出载体PIN家族研究进展 总被引:1,自引:0,他引:1
生长素极性运输调控植物的生长发育。生长素极性运输主要依赖3类转运蛋白: AUX/LAX、PIN和ABCB蛋白家族。生长素在细胞间流动的方向与PIN蛋白在细胞上的极性定位密切相关。PIN蛋白由1个中心亲水环和2个由中心亲水环隔开的疏水区组成。中心亲水环上含多个磷酸化位点,其为一些蛋白激酶的靶点。PIN蛋白受多方面调控,包... 相似文献