全文获取类型
收费全文 | 165413篇 |
免费 | 11949篇 |
国内免费 | 9726篇 |
出版年
2023年 | 2614篇 |
2022年 | 3740篇 |
2021年 | 4925篇 |
2020年 | 5077篇 |
2019年 | 6956篇 |
2018年 | 6066篇 |
2017年 | 4606篇 |
2016年 | 4543篇 |
2015年 | 5183篇 |
2014年 | 9112篇 |
2013年 | 12011篇 |
2012年 | 7061篇 |
2011年 | 9083篇 |
2010年 | 7084篇 |
2009年 | 8149篇 |
2008年 | 8449篇 |
2007年 | 8669篇 |
2006年 | 7766篇 |
2005年 | 6772篇 |
2004年 | 6051篇 |
2003年 | 5231篇 |
2002年 | 4717篇 |
2001年 | 3450篇 |
2000年 | 2819篇 |
1999年 | 2659篇 |
1998年 | 2575篇 |
1997年 | 2261篇 |
1996年 | 2097篇 |
1995年 | 1991篇 |
1994年 | 1901篇 |
1993年 | 1570篇 |
1992年 | 1542篇 |
1991年 | 1400篇 |
1990年 | 1114篇 |
1989年 | 1077篇 |
1988年 | 935篇 |
1987年 | 934篇 |
1986年 | 849篇 |
1985年 | 1337篇 |
1984年 | 1869篇 |
1983年 | 1428篇 |
1982年 | 1562篇 |
1981年 | 1239篇 |
1980年 | 1134篇 |
1979年 | 1035篇 |
1978年 | 809篇 |
1977年 | 730篇 |
1976年 | 690篇 |
1975年 | 479篇 |
1973年 | 487篇 |
排序方式: 共有10000条查询结果,搜索用时 31 毫秒
271.
The abundance of an mRNA encoding an HMG1/2 protein from Pharbitis nil (HMG1) has been previously shown to be regulated by light and an endogenous rhythm in cotyledons. A second Pharbitis nil HMG cDNA (HMG2) was characterized. The sequence of HMG2 was 82% and 86% identical to HMG1 at the nucleotide and amino acid level, respectively. As with HMG1, HMG2 mRNA was detected in all vegetative tissues and was most abundant in roots. However, unlike HMG1, HMG2 mRNA abundance did not increase upon transfer of cotyledons to darkness and did not exhibit regulation by an endogenous circadian rhythm when maintained in continuous darkness over a 68 h period. Similarly, while the abundance of HMG1 mRNA during a dark period that induced photoperiodically controlled flowering was dramatically affected by brief light exposure (night break), this treatment had no effect on HMG2 mRNA abundance. Collectively, these data are consistent with a role of HMG1 in contributing to the circadian-regulated and/or dark-regulated gene expression with constitutive expression of HMG2 playing a housekeeping role in the general regulation of gene expression in Pharbitis nil cotyledons. 相似文献
272.
Shadia Beaini Youakim Saliba Joelle Hajal Viviane Smayra Jules-Joel Bakhos Najat Joubran Dania Chelala Nassim Fares 《Journal of cellular physiology》2019,234(6):9616-9630
Salt-sensitive hypertension is a major risk factor for renal impairment leading to chronic kidney disease. High-salt diet leads to hypertonic skin interstitial volume retention enhancing the activation of the tonicity-responsive enhancer-binding protein (TonEBP) within macrophages leading to vascular endothelial growth factor C (VEGF-C) secretion and NOS3 modulation. This promotes skin lymphangiogenesis and blood pressure regulation. Whether VEGF-C administration enhances renal and skin lymphangiogenesis and attenuates renal damage in salt-sensitive hypertension remains to be elucidated. Hypertension was induced in BALB/c mice by a high-salt diet. VEGF-C was administered subcutaneously to high-salt-treated mice as well as control animals. Analyses of kidney injury, inflammation, fibrosis, and biochemical markers were performed in vivo. VEGF-C reduced plasma inflammatory markers in salt-treated mice. In addition, VEGF-C exhibited a renal anti-inflammatory effect with the induction of macrophage M2 phenotype, followed by reductions in interstitial fibrosis. Antioxidant enzymes within the kidney as well as urinary RNA/DNA damage markers were all revelatory of abolished oxidative stress under VEGF-C. Furthermore, VEGF-C decreased the urinary albumin/creatinine ratio and blood pressure as well as glomerular and tubular damages. These improvements were associated with enhanced TonEBP, NOS3, and lymphangiogenesis within the kidney and skin. Our data show that VEGF-C administration plays a major role in preserving renal histology and reducing blood pressure. VEGF-C might constitute an interesting potential therapeutic target for improving renal remodeling in salt-sensitive hypertension. 相似文献
273.
274.
275.
276.
277.
Wei Liu Yaoting Sun Weigang Ge Fangfei Zhang Lin Gan Yi Zhu Tiannan Guo Kexin Liu 《Molecular & cellular proteomics : MCP》2022,21(2):100187
Drug resistance is a critical obstacle to effective treatment in patients with chronic myeloid leukemia. To understand the underlying resistance mechanisms in response to imatinib mesylate (IMA) and adriamycin (ADR), the parental K562 cells were treated with low doses of IMA or ADR for 2 months to generate derivative cells with mild, intermediate, and severe resistance to the drugs as defined by their increasing resistance index. PulseDIA-based (DIA [data-independent acquisition]) quantitative proteomics was then employed to reveal the proteome changes in these resistant cells. In total, 7082 proteins from 98,232 peptides were identified and quantified from the dataset using four DIA software tools including OpenSWATH, Spectronaut, DIA-NN, and EncyclopeDIA. Sirtuin signaling pathway was found to be significantly enriched in both ADR-resistant and IMA-resistant K562 cells. In particular, isocitrate dehydrogenase (NADP(+)) 2 was identified as a potential drug target correlated with the drug resistance phenotype, and its inhibition by the antagonist AGI-6780 reversed the acquired resistance in K562 cells to either ADR or IMA. Together, our study has implicated isocitrate dehydrogenase (NADP(+)) 2 as a potential target that can be therapeutically leveraged to alleviate the drug resistance in K562 cells when treated with IMA and ADR. 相似文献
278.
J-H Kim K W Park E-W Lee W-S Jang J Seo S Shin K-A Hwang J Song 《Cell death and differentiation》2014,21(4):594-603
The central regulator of adipogenesis, PPARγ, is a nuclear receptor that is linked to obesity and metabolic diseases. Here we report that MKRN1 is an E3 ligase of PPARγ that induces its ubiquitination, followed by proteasome-dependent degradation. Furthermore, we identified two lysine sites at 184 and 185 that appear to be targeted for ubiquitination by MKRN1. Stable overexpression of MKRN1 reduced PPARγ protein levels and suppressed adipocyte differentiation in 3T3-L1 and C3H10T1/2 cells. In contrast, MKRN1 depletion stimulated adipocyte differentiation in these cells. Finally, MKRN1 knockout MEFs showed an increased capacity for adipocyte differentiation compared with wild-type MEFs, with a concomitant increase of PPARγ and adipogenic markers. Together, these data indicate that MKRN1 is an elusive PPARγ E3 ligase that targets PPARγ for proteasomal degradation by ubiquitin-dependent pathways, and further depict MKRN1 as a novel target for diseases involving PPARγ. 相似文献
279.
J.J. Virgen-Ortíz V. Ibarra-Junquera P. Escalante-Minakata J.A. Osuna-Castro J. de J. Ornelas-Paz N.A. Mancilla-Margalli R.L. Castañeda-Aguilar 《Analytical biochemistry》2013
This work presents a rapid and simple freeze centrifugation method to concentrate dilute protein solutions for detection by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS–PAGE) Coomassie blue staining. Moreover, a simple way to assemble a cryoconcentration device is presented, and its use is discussed. Commercial purified protein standard and an enzyme with high fructosyltransferase (FTase) activity, coming from target fractions obtained by chromatographic separation, were used as an example. FTase, coming directly from the chromatographic fractions, was difficult to view through SDS–PAGE analysis; however, it was easily visualized, and its activity was enhanced, after the application of the freeze centrifugation protocol presented here. 相似文献
280.