全文获取类型
收费全文 | 6681篇 |
免费 | 583篇 |
国内免费 | 6篇 |
出版年
2023年 | 17篇 |
2022年 | 68篇 |
2021年 | 166篇 |
2020年 | 86篇 |
2019年 | 95篇 |
2018年 | 164篇 |
2017年 | 128篇 |
2016年 | 216篇 |
2015年 | 360篇 |
2014年 | 408篇 |
2013年 | 467篇 |
2012年 | 588篇 |
2011年 | 525篇 |
2010年 | 321篇 |
2009年 | 251篇 |
2008年 | 402篇 |
2007年 | 387篇 |
2006年 | 315篇 |
2005年 | 314篇 |
2004年 | 304篇 |
2003年 | 211篇 |
2002年 | 221篇 |
2001年 | 208篇 |
2000年 | 144篇 |
1999年 | 114篇 |
1998年 | 53篇 |
1997年 | 39篇 |
1996年 | 45篇 |
1995年 | 34篇 |
1994年 | 32篇 |
1993年 | 23篇 |
1992年 | 56篇 |
1991年 | 36篇 |
1990年 | 39篇 |
1989年 | 34篇 |
1988年 | 31篇 |
1987年 | 37篇 |
1986年 | 24篇 |
1985年 | 24篇 |
1984年 | 19篇 |
1983年 | 17篇 |
1982年 | 20篇 |
1981年 | 22篇 |
1980年 | 16篇 |
1979年 | 21篇 |
1978年 | 20篇 |
1977年 | 22篇 |
1976年 | 20篇 |
1974年 | 17篇 |
1969年 | 13篇 |
排序方式: 共有7270条查询结果,搜索用时 31 毫秒
991.
992.
Keng-Thye Woo Choong-Meng Chan Hui-Lin Choong Han-Kim Tan Marjorie Foo Evan J. C. Lee Chorh-Chuan Tan Grace S. L. Lee Seng-Hoe Tan A. Vathsala Cheng-Hong Lim Gilbert S. C. Chiang Stephanie Fook-Chong Zhao Yi H. B. Tan Kok-Seng Wong 《The HUGO journal》2008,2(3-4):83-91
Background/aims Several studies have reported varying results of the influence of ACE gene on ACEI/ARB therapy. The efficacy of high dose ARB and its influence on ACE gene have not been explored. This is a 6 year randomised trial in IgA nephritis comparing high dose ARB (Losartan 200 mg/day) with normal dose ARB (Losartan 100 mg/day), normal dose ACEI (20 mg/day) and low dose ACEI (10 mg/day). Results Patients on high dose ARB had significantly lower proteinuria, 1.0 ± 0.8 gm/day compared to 1.7 ± 1.0 g/day in the other groups (P = 0.0005). The loss in eGFR was 0.7 ml min?1year?1 for high dose ARB compared to 3.2–3.5 ml min?1year?1 for the other three groups (P = 0.0005). There were more patients on high dose ARB with improvement in eGFR compared to other three groups (P < 0.001). Comparing patients with the three ACE genotypes DD, ID and II, all three groups responded well to therapy with decrease in proteinuria (P < 0.002). Only those on low dose ACEI (10 mg/day) with the I allele had increased in ESRF (P = 0.037). Conclusion High dose ARB is more efficacious in reducing proteinuria and preserving renal function when compared with normal dose ARB and ACEI, and also obviates the genomic influence of ACE gene polymorphism on renal survival. 相似文献
993.
994.
Jang MS Sul JW Choi BJ Lee SJ Suh JH Kim NS Kim WH Lim DS Lee CW Kim E 《The Journal of biological chemistry》2008,283(47):32344-32351
This study reports that Aurora-A (Aur-A) phosphorylates Fas-associated factor-1 (FAF1) at Ser-289 and Ser-291. Forced expression of a FAF1 mutant mimicking phosphorylation at Ser-289 and Ser-291 (FAF1 DD), but not phosphorylation-deficient FAF1 (FAF1 AA), reduced Aur-A expression. However, transfection of FAF1 DD failed to reduce Aur-A expression in the presence of MG132 and MG115, indicating that this decrease is proteasome-mediated. Additionally, transfection of FAF1 DD suppressed the expression of Aur-A in ts20-BALB cells lacking E1 ubiquitin (Ub) activating enzyme activity at restrictive temperatures and also reduced the expression of Aur-A S51D, a mutant resistant to Ub-dependent degradation. Our data indicate that phosphorylated FAF1 mediates the ubiquitin-independent, proteasome-dependent degradation of Aur-A. Overexpression of FAF1 DD blocked Aur-A-induced centrosome amplification and accumulated cells in G(2)/M phase, representing cellular phenotypes consistent with the anticipated loss of Aur-A. Collectively, our findings support the negative feedback regulation of Aur-A via phosphorylation of the death-promoting protein, FAF1, and disclose the presence of molecular cross-talk between constituents of the cell cycle and cell death machinery. 相似文献
995.
Eudes A Bozzo GG Waller JC Naponelli V Lim EK Bowles DJ Gregory JF Hanson AD 《The Journal of biological chemistry》2008,283(22):15451-15459
Plants produce p-aminobenzoate (pABA) in chloroplasts and use it for folate synthesis in mitochondria. In plant tissues, however, pABA is known to occur predominantly as its glucose ester (pABA-Glc), and the role of this metabolite in folate synthesis has not been defined. In this study, the UDP-glucose:pABA acyl-glucosyltransferase (pAGT) activity in Arabidopsis extracts was found to reside principally (95%) in one isoform with an apparent K(m) for pABA of 0.12 mm. Screening of recombinant Arabidopsis UDP-glycosyltransferases identified only three that recognized pABA. One of these (UGT75B1) exhibited a far higher k(cat)/K(m) value than the others and a far lower apparent K(m) for pABA (0.12 mm), suggesting its identity with the principal enzyme in vivo. Supporting this possibility, ablation of UGT75B1 reduced extractable pAGT activity by 95%, in vivo [(14)C]pABA glucosylation by 77%, and the endogenous pABA-Glc/pABA ratio by 9-fold. The K(eq) for the pABA esterification reaction was found to be 3 x 10(-3). Taken with literature data on the cytosolic location of pAGT activity and on cytosolic UDP-glucose/UDP ratios, this K(eq) value allowed estimation that only 4% of cytosolic pABA is esterified. That pABA-Glc predominates in planta therefore implies that it is sequestered away from the cytosol and, consistent with this possibility, vacuoles isolated from [(14)C]pABA-fed pea leaves were estimated to contain> or =88% of the [(14)C]pABA-Glc formed. In total, these data and the fact that isolated mitochondria did not take up [(3)H]pABA-Glc, suggest that the glucose ester represents a storage form of pABA that does not contribute directly to folate synthesis. 相似文献
996.
997.
998.
Tomato phenylalanine ammonia-lyase gene family, highly redundant but strongly underutilized 总被引:4,自引:0,他引:4
999.
1000.
Functional differences of the catalytic and non-catalytic domains in human ADAMTS-4 and ADAMTS-5 in aggrecanolytic activity 总被引:2,自引:0,他引:2
Fushimi K Troeberg L Nakamura H Lim NH Nagase H 《The Journal of biological chemistry》2008,283(11):6706-6716
ADAMTS-4 (aggrecanase-1) and ADAMTS-5 (aggrecanase-2) are multidomain metalloproteinases belonging to the ADAMTS family. We have previously reported that human ADAMTS-5 has much higher aggrecanolytic activity than human ADAMTS-4. To investigate the different proteolytic activity of the two enzymes, we generated a series of chimeras by exchanging various non-catalytic domains of the two proteinases. We found that the catalytic domain of ADAMTS-5 has higher intrinsic catalytic ability than that of ADAMTS-4. The studies also demonstrated that the non-catalytic domains of ADAMTS-5 are more effective modifiers than those of ADAMTS-4, making both catalytic domains more active against aggrecan, an Escherichia coli-expressed interglobular domain of aggrecan and fibromodulin. Addition of the C-terminal thrombospondin type I motif of ADAMTS-5 to the C terminus of ADAMTS-4 increased the activity of ADAMTS-4 against aggrecan and fibromodulin severalfold. In contrast to previous reports (Kashiwagi, M., Enghild, J. J., Gendron, C., Hughes, C., Caterson, B., Itoh, Y., and Nagase, H. (2004) J. Biol. Chem. 279, 10109-10119 and Gao, G., Plaas, A., Thompson, V. P., Jin, S., Zuo, F., and Sandy, J. D. (2004) J. Biol. Chem. 279, 10042-10051), our detailed investigation of the role of the C-terminal spacer domain of ADAMTS-4 indicated that full-length ADAMTS-4 is approximately 20-times more active against aggrecan than its spacer domain deletion mutant, even at the Glu373-Ala374 site of the interglobular domain. This discrepancy is most likely due to selective inhibition of full-length ADAMTS-4 by heparin, particularly for cleavage at the Glu373-Ala374 bond. However, removal of the spacer domain from ADAMTS-4 greatly enhanced more general proteolytic activity against non-aggrecan substrates, e.g. E. coli-expressed interglobular domain, fibromodulin, and carboxymethylated transferrin. 相似文献