全文获取类型
收费全文 | 9586篇 |
免费 | 694篇 |
国内免费 | 4篇 |
出版年
2024年 | 3篇 |
2023年 | 36篇 |
2022年 | 31篇 |
2021年 | 181篇 |
2020年 | 151篇 |
2019年 | 204篇 |
2018年 | 256篇 |
2017年 | 276篇 |
2016年 | 437篇 |
2015年 | 616篇 |
2014年 | 695篇 |
2013年 | 735篇 |
2012年 | 919篇 |
2011年 | 904篇 |
2010年 | 589篇 |
2009年 | 474篇 |
2008年 | 635篇 |
2007年 | 571篇 |
2006年 | 492篇 |
2005年 | 439篇 |
2004年 | 371篇 |
2003年 | 326篇 |
2002年 | 265篇 |
2001年 | 119篇 |
2000年 | 115篇 |
1999年 | 80篇 |
1998年 | 52篇 |
1997年 | 31篇 |
1996年 | 25篇 |
1995年 | 26篇 |
1994年 | 16篇 |
1993年 | 15篇 |
1992年 | 23篇 |
1991年 | 22篇 |
1990年 | 14篇 |
1989年 | 20篇 |
1988年 | 17篇 |
1987年 | 7篇 |
1986年 | 9篇 |
1985年 | 17篇 |
1984年 | 11篇 |
1983年 | 5篇 |
1982年 | 8篇 |
1979年 | 9篇 |
1978年 | 4篇 |
1976年 | 3篇 |
1975年 | 5篇 |
1974年 | 6篇 |
1973年 | 4篇 |
1972年 | 4篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
1.
Jung Mi Lim Kyung S. Lee Hyun Ae Woo Dongmin Kang Sue Goo Rhee 《The Journal of cell biology》2015,210(1):935-945
Proteins associated with the centrosome play key roles in mitotic progression in mammalian cells. The activity of Cdk1-opposing phosphatases at the centrosome must be inhibited during early mitosis to prevent premature dephosphorylation of Cdh1—an activator of the ubiquitin ligase anaphase-promoting complex/cyclosome—and the consequent premature degradation of mitotic activators. In this paper, we show that reversible oxidative inactivation of centrosome-bound protein phosphatases such as Cdc14B by H2O2 is likely responsible for this inhibition. The intracellular concentration of H2O2 increases as the cell cycle progresses. Whereas the centrosome is shielded from H2O2 through its association with the H2O2-eliminating enzyme peroxiredoxin I (PrxI) during interphase, the centrosome-associated PrxI is selectively inactivated through phosphorylation by Cdk1 during early mitosis, thereby exposing the centrosome to H2O2 and facilitating inactivation of centrosome-bound phosphatases. Dephosphorylation of PrxI by okadaic acid–sensitive phosphatases during late mitosis again shields the centrosome from H2O2 and thereby allows the reactivation of Cdk1-opposing phosphatases at the organelle. 相似文献
2.
Molecular Biology Reports - We present here on an innovative assay for detecting miRNAs using a uniquely designed specific extension sequence that provides high efficiency and accuracy. This assay... 相似文献
3.
Pasupathi Sundaramoorthy Jae Jun Sim Yeong-Su Jang Siddhartha Kumar Mishra Keun-Yeong Jeong Poonam Mander Oh Byung Chul Won-Sik Shim Seung Hyun Oh Ky-Youb Nam Hwan Mook Kim 《PloS one》2015,10(1)
Cancer cell motility is a key phenomenon regulating invasion and metastasis. Focal adhesion kinase (FAK) plays a major role in cellular adhesion and metastasis of various cancers. The relationship between dietary supplementation of calcium and colon cancer has been extensively investigated. However, the effect of calcium (Ca2+) supplementation on calpain-FAK-motility is not clearly understood. We sought to identify the mechanism of FAK cleavage through Ca2+ bound lactate (CaLa), its downstream signaling and role in the motility of human colon cancer cells. We found that treating HCT116 and HT-29 cells with CaLa immediately increased the intracellular Ca2+ (iCa2+) levels for a prolonged period of time. Ca2+ influx induced cleavage of FAK into an N-terminal FAK (FERM domain) in a dose-dependent manner. Phosphorylated FAK (p-FAK) was also cleaved in to its p-N-terminal FAK. CaLa increased colon cancer cells motility. Calpeptin, a calpain inhibitor, reversed the effects of CaLa on FAK and pFAK cleavage in both cancer cell lines. The cleaved FAK translocates into the nucleus and modulates p53 stability through MDM2-associated ubiquitination. CaLa-induced Ca2+ influx increased the motility of colon cancer cells was mediated by calpain activity through FAK and pFAK protein destabilization. In conclusion, these results suggest that careful consideration may be given in deciding dietary Ca2+ supplementation to patient undergoing treatment for metastatic cancer. 相似文献
4.
Theoretical calculation of the sugar concentrations during enzymatic production of fructooligosaccharides 总被引:1,自引:0,他引:1
Summary In a batch production of fructooligosaccharides from sucrose, the concentrations of residual sucrose, glucose and fructooligosaccharides at a given reaction time(t) and initial sucrose concentration(S0) were theoretically calculated by the following correlation equations: Glucose(t) = 0.0653 S0 × ln(t); Fructooligosaccharides(t) = 0.1636 S0 × ln(t); Sucrose(t)=S0 - Glucose(t) + FOS(t). 相似文献
5.
6.
In our previous studies, we observed the biological control effect of lactic acid bacteria strains (LABs) KLF01, KLC02 and KPD03 against different plant pathogenic bacteria in vitro against Ralstonia solanacearum, and strains KLF01 and KLC02 against Pectobacterium carotovorum under greenhouse and field experiments, respectively. In this study, we observed the efficacy of these bacteria against bacterial spot pathogen (Xanthomonas campestris pv. vesicatoria) and their plant growth-promoting activities in pepper (Capsicum annuum L. var. annuum), under greenhouse and field conditions. LABs significantly (P < 0.05) reduced bacterial spot on pepper plants in comparison to untreated plants in both the greenhouse and the field experiments. The plant growth-promoting effect of LABs on pepper varied; some strains had a significant effect on growth promotion (P < 0.05) compared with untreated plants, while some showed no significant effect in the greenhouse and field experiments. Additionally, LABs were able to colonise roots, produce indole-3-acetic acid (IAA), siderophores and solubilise phosphate. These findings indicate that application of LABs could provide a promising alternative for the management of bacterial spot disease in pepper plants and could therefore be used as a healthy plant growth-promoting agent. 相似文献
7.
8.
Hyun Soo Lee Romerson D. Dimla Peter G. Schultz 《Bioorganic & medicinal chemistry letters》2009,19(17):5222-5224
The photo-crosslinking amino acid, p-benzoyl-l-phenylalanine (pBpa), was genetically incorporated into Escherichia coli catabolite activator protein (CAP) in bacteria in response to an amber nonsense codon using an orthogonal tRNA/aminoacyl-tRNA synthetase pair. The mutant CAP (CAP-K26Bpa) containing pBpa formed a covalent complex with a DNA fragment containing the consensus operator sequence upon UV irradiation. Because this amino acid can be genetically incorporated into any DNA-binding protein in E. coli, yeast or mammalian cells with minimal perturbation of protein structure, this method should be generally useful for investigating DNA–protein interactions. 相似文献
9.
Dong Hyun Jo Chang Sik Cho Jin Hyoung Kim Hyoung Oh Jun Jeong Hun Kim 《Journal of biomedical science》2013,20(1):38
Effective and validated animal models are valuable to investigate the pathogenesis and potential therapeutics for human diseases. There is much concern for diabetic retinopathy (DR) in that it affects substantial number of working population all around the world, resulting in visual deterioration and social deprivation. In this review, we discuss animal models of DR based on different species of animals from zebrafish to monkeys and prerequisites for animal models. Despite criticisms on imprudent use of laboratory animals, we hope that animal models of DR will be appropriately utilized to deepen our understanding on the pathogenesis of DR and to support our struggle to find novel therapeutics against catastrophic visual loss from DR. 相似文献
10.
Abstract The syntheses of three classes of adenosine analogues involving cyclosubstitution at the 6-position and functionalization at the 2-position are reported. The target molecules synthesized are stable with respect to hydrolytic deamination by mammalian adenosine deaminase, and, because of major structural changes at the 2- and 6-positions, these compounds are expected to be poor phosphorylation substrates for the kinases. Adenosine receptor binding data reveal that several of the compounds synthesized show excellent A1 receptor affinity and A2/A1 selectivity. 相似文献