全文获取类型
收费全文 | 667篇 |
免费 | 41篇 |
出版年
2023年 | 1篇 |
2022年 | 4篇 |
2021年 | 7篇 |
2020年 | 5篇 |
2019年 | 10篇 |
2018年 | 8篇 |
2017年 | 11篇 |
2016年 | 11篇 |
2015年 | 32篇 |
2014年 | 28篇 |
2013年 | 49篇 |
2012年 | 46篇 |
2011年 | 50篇 |
2010年 | 21篇 |
2009年 | 22篇 |
2008年 | 36篇 |
2007年 | 40篇 |
2006年 | 33篇 |
2005年 | 34篇 |
2004年 | 40篇 |
2003年 | 36篇 |
2002年 | 39篇 |
2001年 | 6篇 |
2000年 | 9篇 |
1999年 | 8篇 |
1998年 | 7篇 |
1997年 | 9篇 |
1996年 | 5篇 |
1995年 | 11篇 |
1994年 | 3篇 |
1993年 | 8篇 |
1992年 | 8篇 |
1991年 | 7篇 |
1990年 | 11篇 |
1989年 | 4篇 |
1988年 | 4篇 |
1987年 | 5篇 |
1986年 | 4篇 |
1985年 | 4篇 |
1984年 | 6篇 |
1983年 | 3篇 |
1982年 | 3篇 |
1981年 | 2篇 |
1980年 | 1篇 |
1979年 | 7篇 |
1978年 | 4篇 |
1975年 | 3篇 |
1974年 | 2篇 |
1970年 | 1篇 |
排序方式: 共有708条查询结果,搜索用时 15 毫秒
31.
Thienopyridine and benzofuran derivatives as potent anti-tumor agents possessing different structure-activity relationships 总被引:1,自引:0,他引:1
Hayakawa I Shioya R Agatsuma T Furukawa H Sugano Y 《Bioorganic & medicinal chemistry letters》2004,14(13):3411-3414
(3-Amino-6-thiophen-2-yl-thieno[2,3-b]pyridin-2-yl)phenylmethanone (3) was discovered as a new type of cytotoxic agent selective against a tumorigenic cell line. The molecular structure of a previously reported compound, (4-hydroxy-3-methyl-6-phenylbenzofuran-2-yl)phenylmethanone (2), had remarkably similar bioisosteric substructures to that of compound 3. Although the relationship between the molecular structure and biological activity of each derivative synthesized from these two hit compounds (2 and 3) were studied, unexpectedly no correlation was observed. However, after further synthetic study from 3, one of the most potent derivative (10k) having a different SAR profile from 2, was discovered. 相似文献
32.
Vascular dysfunction is a hallmark of many diseases, including coronary heart disease, stroke and diabetes. The underlying mechanisms of these disorders, which are intimately associated with inflammation and oxidative stress caused by excess reactive oxygen species (ROS), have remained elusive. Here we report that ROS are powerful inhibitors of vascular smooth muscle calcium-dependent Slo1 BK or Maxi-K potassium channels, an important physiological determinant of vascular tone. By targeting a cysteine residue near the Ca(2+) bowl of the BK alpha subunit, H(2)O(2) virtually eliminates physiological activation of the channel, with an inhibitory potency comparable to a knockout of the auxiliary subunit BK beta 1. These results reveal a molecular structural basis for the vascular dysfunction involving oxidative stress and provide a solid rationale for a potential use of BK openers in the prevention and treatment of cardiovascular disorders. 相似文献
33.
Bowen BW Bass AL Chow SM Bostrom M Bjorndal KA Bolten AB Okuyama T Bolker BM Epperly S Lacasella E Shaver D Dodd M Hopkins-Murphy SR Musick JA Swingle M Rankin-Baransky K Teas W Witzell WN Dutton PH 《Molecular ecology》2004,13(12):3797-3808
Juvenile loggerhead turtles (Caretta caretta) from West Atlantic nesting beaches occupy oceanic (pelagic) habitats in the eastern Atlantic and Mediterranean, whereas larger juvenile turtles occupy shallow (neritic) habitats along the continental coastline of North America. Hence the switch from oceanic to neritic stage can involve a trans-oceanic migration. Several researchers have suggested that at the end of the oceanic phase, juveniles are homing to feeding habitats in the vicinity of their natal rookery. To test the hypothesis of juvenile homing behaviour, we surveyed 10 juvenile feeding zones across the eastern USA with mitochondrial DNA control region sequences (N = 1437) and compared these samples to potential source (nesting) populations in the Atlantic Ocean and Mediterranean Sea (N = 465). The results indicated a shallow, but significant, population structure of neritic juveniles (PhiST = 0.0088, P = 0.016), and haplotype frequency differences were significantly correlated between coastal feeding populations and adjacent nesting populations (Mantel test R2 = 0.52, P = 0.001). Mixed stock analyses (using a Bayesian algorithm) indicated that juveniles occurred at elevated frequency in the vicinity of their natal rookery. Hence, all lines of evidence supported the hypothesis of juvenile homing in loggerhead turtles. While not as precise as the homing of breeding adults, this behaviour nonetheless places juvenile turtles in the vicinity of their natal nesting colonies. Some of the coastal hazards that affect declining nesting populations may also affect the next generation of turtles feeding in nearby habitats. 相似文献
34.
Previously, three arabinan-degrading enzymes were isolated from Penicillium chrysogenum 31B. Here we describe another arabinan-degrading enzyme, termed Abnc, from the culture filtrate of the same organism. Analysis of the reaction products of debranched arabinan by high-performance anion-exchange chromatography (HPAEC) revealed that Abnc cleaved the substrate in an endo manner and that the final major product was arabinotriose. The molecular mass of Abnc was estimated to be 35 kDa by SDS-PAGE. Enzyme activity of Abnc was highest at pH 6.0 to 7.0. The enzyme was stable up to 30 degrees C and showed optimum activity at 30 to 40 degrees C. Compared with a mesophilic counterpart from Aspergillus niger, Abnc exhibited a lower thermal stability and optimum enzyme activity at lower temperatures. Production of Abnc in P. chrysogenum was found to be strongly induced by arabinose-containing polymers and required a longer culture time than did other arabinanase isozymes in this strain. 相似文献
35.
36.
37.
Fenitroxon insensitive acetylcholinesterases of the housefly, Musca domestica associated with point mutations 总被引:7,自引:0,他引:7
The cDNA of AChE in the housefly, Musca domestica, was sequenced and individual flies were genotyped by this gene in an inhibition assay of AChE activity with an organophaspate, fenitroxon. Mutations at Gly(342) and Tyr(407), which are reportedly conserved in resistant strains of Drosophila, were associated with the insensitivity to fenitroxon. Two other mutations, Ile(162) and Val(260), did not have an apparent effect on insensitivity. However, the four mutations are located in the active site of the enzyme, and therefore the non-neutral mutations in this gene are considered to cause the insensitivity of AChE in the development of insecticide resistance of the housefly. 相似文献
38.
39.
For the purpose of providing biologically stable building blocks for the biocombinatorial synthesis using a living cell, some ether-linked alkyl 5a-carba-beta-D-glycoside primers were prepared. The key step of the synthesis was coupling of 1-bromo-n-alkanes with the 1-OH unprotected derivatives of 5a-carba-sugar analogues of D-glucose, D-galactose, and 2-acetamido-2-deoxy-D-glucose (N-acetyl-D-glucosamine), in DMF in the presence of sodium hydride. Alternatively, alkyl carba-lactoside was synthesized by incorporation of a 5a-carba-beta-D-galactose residue into the 4-position of dodecyl beta-D-glucopyranoside. A strong and specific inhibition of beta-galactosidase (K(i) 0.67 microM, bovine liver) was found for dodecyl 5a-carba-beta-D-galactopyranoside. 相似文献
40.