全文获取类型
收费全文 | 2936篇 |
免费 | 156篇 |
专业分类
3092篇 |
出版年
2023年 | 7篇 |
2022年 | 26篇 |
2021年 | 49篇 |
2020年 | 15篇 |
2019年 | 30篇 |
2018年 | 46篇 |
2017年 | 33篇 |
2016年 | 54篇 |
2015年 | 92篇 |
2014年 | 93篇 |
2013年 | 225篇 |
2012年 | 186篇 |
2011年 | 182篇 |
2010年 | 119篇 |
2009年 | 111篇 |
2008年 | 196篇 |
2007年 | 204篇 |
2006年 | 195篇 |
2005年 | 162篇 |
2004年 | 205篇 |
2003年 | 159篇 |
2002年 | 155篇 |
2001年 | 51篇 |
2000年 | 61篇 |
1999年 | 40篇 |
1998年 | 46篇 |
1997年 | 27篇 |
1996年 | 17篇 |
1995年 | 24篇 |
1994年 | 13篇 |
1993年 | 21篇 |
1992年 | 33篇 |
1991年 | 34篇 |
1990年 | 16篇 |
1989年 | 20篇 |
1988年 | 16篇 |
1987年 | 7篇 |
1986年 | 17篇 |
1985年 | 7篇 |
1984年 | 9篇 |
1983年 | 10篇 |
1982年 | 8篇 |
1979年 | 9篇 |
1978年 | 6篇 |
1976年 | 5篇 |
1975年 | 9篇 |
1973年 | 8篇 |
1972年 | 4篇 |
1968年 | 5篇 |
1967年 | 6篇 |
排序方式: 共有3092条查询结果,搜索用时 31 毫秒
911.
Although it is well established that Ras requires membrane localization for activation of its target molecule, Raf-1, the reason for this requirement is not fully understood. In this study, we found that modified Ras, which is purified from Sf9 cells, could activate Raf-1 in a cell-free system, when incorporated into liposome. Using a bifunctional cross-linker and a protein-fragmentation complementation assay, we detected dimer formation of Ras in the liposome and in the intact cells, respectively. These results suggest that dimerization of Ras in the lipid membrane is essential for activation of Raf-1. To support this, we found that, when fused to glutathione S-transferase (GST), unprocessed Ras expressed in Escherichia coli could bypass the requirement for liposome. A Ras-dependent Raf-1 activator, which we previously reported (Mizutani, S., Koide, H., and Kaziro, Y. (1998) Oncogene 16, 2781-2786), was still required for Raf-1 activation by GST-Ras. Furthermore, an enforced dimerization of unmodified oncogenic Ras mutant in human embryonic kidney (HEK) 293 cells, using a portion of gyrase B or estrogen receptor, also resulted in activation of Raf-1. From these results, we conclude that membrane localization allows Ras to form a dimer, which is essential, although not sufficient, for Raf-1 activation. 相似文献
912.
Hiraguri A Itoh R Kondo N Nomura Y Aizawa D Murai Y Koiwa H Seki M Shinozaki K Fukuhara T 《Plant molecular biology》2005,57(2):173-188
Proteins that specifically bind double-stranded RNA (dsRNA) are involved in the regulation of cellular signaling events and gene expression, and are characterized by a conserved dsRNA-binding motif (dsRBM). Here we report the biochemical properties of nine such gene products, each containing one or two dsRBMs: four ArabidopsisDicer-like proteins (DCL1-4), ArabidopsisHYL1 and four of its homologs (DRB2, DRB4, DRB5 and OsDRB1). DCL1, DCL3, HYL1 and the four HYL1 homologs exhibit significant dsRNA-binding activity, indicating that these proteins are involved in RNA metabolism. The dsRBMs from dsRBM-containing proteins (dsRBPs) also function as a protein–protein interaction domain and homo- and heterodimerization are essential for biological functioning of these proteins. We show that DRB4 interacts specifically with DCL4, and HYL1 most strongly interacts with DCL1. These results indicate that each HYL1/DRB family protein interacts with one specific partner among the four Dicer-like proteins. Localization studies using GFP fusion proteins demonstrate that DCL1, DCL4, HYL1 and DRB4 localize in the nucleus, while DRB2 is present in the cytoplasm. Subcellular localizations of HYL1, DRB4, DCL1 and DCL4 further strengthen the notion that HYL1 and DCL1, and DRB4 and DCL4, exist as complexes. The presented data suggest that each member of the HYL1/DRB protein family may individually modulate Dicer function through heterodimerization with a Dicer-like protein in vivo. 相似文献
913.
Ueno K Araki Y Hirai N Saito S Mizutani M Sakata K Todoroki Y 《Bioorganic & medicinal chemistry》2005,13(10):3359-3370
A major catabolic enzyme of the plant hormone abscisic acid (ABA) is the cytochrome P450 monooxygenase ABA 8'-hydroxylase. For designing a specific inhibitor of this enzyme, the substrate specificity and inhibition of CYP707A3, an ABA 8'-hydroxylase from Arabidopsis thaliana, was investigated using 45 structural analogues of ABA and compared to the structural requirements for ABA activity. Substrate recognition by the enzyme strictly required the 6'-methyl groups (C-8' and C-9'), which were unnecessary for ABA activity, whereas elimination of the 3-methyl (C-6) and 1'-hydroxyl groups, which significantly affected ABA activity, had little effect on the ability of analogues to competitively inhibit the enzyme. Fluorination at C-8' and C-9' resulted in resistance to 8'-hydroxylation and competitive inhibition of the enzyme. In particular, 8',8'-difluoro-ABA and 9',9'-difluoro-ABA yielded no enzyme reaction products and strongly inhibited the enzyme (K(I) = 0.16 and 0.25 microM, respectively). 相似文献
914.
Iida A Takamatsu N Hori H Wakamatsu Y Shimada A Shima A Koga A 《Pigment cell research / sponsored by the European Society for Pigment Cell Research and the International Pigment Cell Society》2005,18(5):382-384
We have previously identified three naturally occurring mutations in the medaka fish tyrosinase gene caused by transposable element insertions. Tyr-i(b) is one of these, containing the Tol2 element in the promoter region. Its homozygous carriers exhibit a weak oculocutaneous albino phenotype. We report here spontaneous reversion of the albino phenotype to the wild-type pigmentation, associated with excision of the Tol2 element. The newly arising mutant gene is inherited in the Mendelian fashion. Thus, oculocutaneous albinism is not strictly irreversible, at least in this organism and the results also indicate that the insertion of the Tol2 element is the main, and possibly the only, cause of the i(b) albinism. Importantly our data also suggest that medaka fish possess an active transposase. 相似文献
915.
Can statin therapy really reduce the risk of Alzheimer's disease and slow its progression? 总被引:2,自引:0,他引:2
PURPOSE OF REVIEW: Statins are the most used cholesterol-lowering agents worldwide. Earlier studies suggested that they may have preventive effects in Alzheimer's disease. However, prospective studies have questioned this hypothesis. RECENT FINDINGS: Statins regulate beta-amyloid metabolism and microglial activation. Pathologically, patients with Alzheimer's disease have more severe atherosclerosis in cerebral arteries than do controls. Such lesions may cause cerebral hypoperfusion, a risk factor for dementia and cognitive decline. Although most population-based studies have failed to show a beneficial effect of statins in Alzheimer's disease, two randomized controlled trials suggested that statins slow cognitive decline in mild to moderate Alzheimer's disease. SUMMARY: There is still some hope that statins reduce the incidence of Alzheimer's disease and slow its progression. Large-scale randomized controlled trials of simvastatin and atorvastatin for mild to moderate Alzheimer's disease are underway, which might provide more conclusive results than earlier studies. 相似文献
916.
917.
Goto T Shibata A Sasaki D Suzuki N Hishinuma T Kakiyama G Iida T Mano N Goto J 《Steroids》2005,70(3):185-192
We report a novel conjugate, bile acid acyl galactosides, which exist in the urine of healthy volunteers. To identify the two unknown peaks obtained in urine specimens from healthy subjects, the specimens were subjected to solid phase extraction and then to liquid chromatographic separation. The eluate corresponding to the unknown peaks on the chromatogram was collected. Following alkaline hydrolysis and liquid chromatography (LC)/electrospray ionization (ESI)-mass spectrometric (MS) analysis, cholic acid (CA) and deoxycholic acid (DCA) were identified as liberated bile acids. When a portion of the alkaline hydrolyzate was subjected to a derivatization reaction with 1-phenyl-3-methyl-5-pyrazolone, a derivative of galactose was detected by LC/ESI-MS. Finally, the liquid chromatographic and mass spectrometric properties of these unknown compounds in urine specimens were compared to those of authentic specimens and the structures were confirmed as CA 24-galactoside and DCA 24-galactoside. These results strongly imply that bile acid 24-galactosides, a novel conjugate, were synthesized in the human body. 相似文献
918.
Mizutani CM Nie Q Wan FY Zhang YT Vilmos P Sousa-Neves R Bier E Marsh JL Lander AD 《Developmental cell》2005,8(6):915-924
The dorsoventral axis of the Drosophila embryo is patterned by a gradient of bone morphogenetic protein (BMP) ligands. In a process requiring at least three additional extracellular proteins, a broad domain of weak signaling forms and then abruptly sharpens into a narrow dorsal midline peak. Using experimental and computational approaches, we investigate how the interactions of a multiprotein network create the unusual shape and dynamics of formation of this gradient. Starting from observations suggesting that receptor-mediated BMP degradation is an important driving force in gradient dynamics, we develop a general model that is capable of capturing both subtle aspects of gradient behavior and a level of robustness that agrees with in vivo results. 相似文献
919.
920.
A practical asymmetric synthetic route to 4,4,4-trifluoro-3-hydroxybutyrophenone and the butyric acid phenyl ester is described using heterochiral crystallization through double hydrogen bonding assembly in head-to-tail fashion and sequential Baeyer-Villiger oxidation reaction by trifluoroperacetic acid. 相似文献