全文获取类型
收费全文 | 724篇 |
免费 | 56篇 |
国内免费 | 20篇 |
出版年
2023年 | 4篇 |
2022年 | 7篇 |
2021年 | 11篇 |
2020年 | 16篇 |
2019年 | 18篇 |
2018年 | 9篇 |
2017年 | 12篇 |
2016年 | 24篇 |
2015年 | 40篇 |
2014年 | 55篇 |
2013年 | 49篇 |
2012年 | 54篇 |
2011年 | 56篇 |
2010年 | 37篇 |
2009年 | 37篇 |
2008年 | 29篇 |
2007年 | 27篇 |
2006年 | 27篇 |
2005年 | 42篇 |
2004年 | 36篇 |
2003年 | 21篇 |
2002年 | 19篇 |
2001年 | 6篇 |
2000年 | 6篇 |
1999年 | 11篇 |
1998年 | 10篇 |
1997年 | 5篇 |
1996年 | 8篇 |
1995年 | 4篇 |
1993年 | 6篇 |
1992年 | 8篇 |
1991年 | 6篇 |
1990年 | 6篇 |
1989年 | 10篇 |
1988年 | 8篇 |
1987年 | 4篇 |
1986年 | 5篇 |
1985年 | 8篇 |
1984年 | 4篇 |
1983年 | 2篇 |
1982年 | 7篇 |
1980年 | 3篇 |
1979年 | 7篇 |
1978年 | 4篇 |
1977年 | 8篇 |
1974年 | 3篇 |
1973年 | 7篇 |
1972年 | 2篇 |
1971年 | 2篇 |
1968年 | 4篇 |
排序方式: 共有800条查询结果,搜索用时 15 毫秒
1.
2.
眼镜蛇科蛇毒对S180,EAC腹水癌治疗作用研究 总被引:1,自引:0,他引:1
本文报道金环蛇、扁颈蛇、眼镜蛇、银环蛇蛇毒及其细胞毒对小鼠S180,EAC腹水癌的治疗作用。结果表明,蛇毒及其细胞毒在体外有明显杀灭癌细胞作用,体内有较明显的治疗作用,动物存活时间延长,接种率降低。肿瘤细胞呈现不同程度形态变化,主要为膜破裂,坏死等。治疗效应由强到弱为金环蛇毒,扁颈蛇毒,金环蛇细胞毒,眼镜蛇毒,眼镜蛇细胞毒。银环蛇毒无作用。 相似文献
3.
4.
Studies on compound I formation of the lignin peroxidase from Phanerochaete chrysosporium 总被引:2,自引:0,他引:2
Ligninase, isolated from the wood-destroying fungus Phanerochaete chrysosporium, catalyzes the oxidation of lignin and lignin-related compounds. Ligninase reacts with H2O2 to form the classical peroxidase intermediates Compounds I and II. We have determined the activation energy of ligninase Compound I formation to be 5.9 kcal/mol. The effect of pH and ionic strength on the rate of ligninase Compound I formation was studied. In contrast to all other peroxidases, no pH effect was observed. This is despite homology of active-site amino acids residues (Tien, M., and Tu, C.-P. D. (1987) Nature 326, 520-523) which are proposed to affect the pH profile of Compound I formation. Ligninase Compound I formation can also be supported by organic peroxides. The second-order rate constants with the organic peroxides are lower, suggesting that H2O2 is the preferred substrate. 相似文献
5.
Ligninase of Phanerochaete chrysosporium. Mechanism of its degradation of the non-phenolic arylglycerol beta-aryl ether substructure of lignin. 总被引:12,自引:1,他引:11 下载免费PDF全文
This study examined the ligninase-catalysed degradation of lignin model compounds representing the arylglycerol beta-aryl ether substructure, which is the dominant one in the lignin polymer. Three dimeric model compounds were used, all methoxylated in the 3- and 4-positions of the arylglycerol ring (ring A) and having various substituents in the beta-ether-linked aromatic ring (ring B), so that competing reactions involving both rings could be compared. Studies of the products formed and the time courses of their formation showed that these model compounds are oxidized by ligninase (+ H2O2 + O2) in both ring A and ring B. The major consequence with all three model compounds is oxidation of ring A, leading primarily to cleavage between C(alpha) and C(beta) (C(alpha) being proximal to ring A), and to a lesser extent to the oxidation of the C(alpha)-hydroxy group to a carbonyl group. Such C(alpha)-oxidation deactivates ring A, leaving only ring B for attack. Studies with C(alpha)-carbonyl model compounds corresponding to the three basic model compounds revealed that oxidation of ring B leads in part to dealkoxylations (i.e. to cleavage of the glycerol beta-aryl ether bond and to demethoxylations), but that these are minor reactions in the model compounds most closely related to lignin. Evidence is also given that another consequence of oxidation of ring B in the C(alpha)-carbonyl model compounds is formation of unstable cyclohexadienone ketals, which can decompose with elimination of the beta-ether-linked aromatic ring. The mechanisms proposed for the observed reactions involve initial formation of aryl cation radicals in either ring A or ring B. The cation radical intermediate from one of the C(alpha)-carbonyl model compounds was identified by e.s.r. spectroscopy. The mechanisms are based on earlier studies showing that ligninase acts by oxidizing appropriately substituted aromatic nuclei to aryl cation radicals [Kersten, Tien, Kalyanaraman & Kirk (1985) J. Biol. Chem. 260, 2609-2612; Hammel, Tien, Kalyanaraman & Kirk (1985) J. Biol. Chem. 260, 8348-8353]. 相似文献
6.
7.
Bwee Tien Poll-The Ola H. Skjeldal Oddvar Stokke Alf Poulos France Demaugre Jean-Marie Saudubray 《Human genetics》1989,81(2):175-181
Summary We have measured the production of 14CO2 from exogenous [1-14C] phytanic acid in fibroblast monolayers from patients with classical Refsum's disease and peroxisomal disorders. Activities in the different disorders were (percentage of control): classical Refsum's disease (5%), isolated peroxisomal acyl-CoA oxidase deficiency (75%), Zellweger syndrome (4%), neonatal adrenoleukodystrophy (5%), and rhizomelic chondrodysplasia punctate (3%). Absence of complementation was demonstrated between Zellweger syndrome and infantile Refsum's disease lines after polyethylene glycol fusion, with decreases of average activity of 11% relative to unfused cell mixtures. Classical Refsum's disease, rhizomelic chondrodysplasia punctata, and neonatal adrenoleukodystrophy lines all complemented one another, and Zellweger syndrome or infantile Refsum's disease lines, with average activity increases of 522%–772%. No intragenic complementation was observed within either group. Four complementation groups were detected suggesting that at least four genes are involved in phytanic acid -oxidation: one gene for the enzyme phytanic acid -hydroxylase (probably mitochondrial); one gene for a regulatory factor for the expression of phytanic acid -decarboxylation activity and two membrane-bound peroxisomal enzymes involved in the synthesis of plasmalogens; two genes for the assembly of functional peroxisomes and/or import of proteins into peroxisomes. 相似文献
8.
Lignin and veratryl alcohol are not inducers of the ligninolytic system of Phanerochaete chrysosporium. 总被引:5,自引:4,他引:1 下载免费PDF全文
Phanerochaete chrysosporium is a white rot fungus which secretes a family of lignin-degrading enzymes under nutrient limitation. In this work, we investigated the roles of veratryl alcohol and lignin in the ligninolytic system of P. chrysosporium BKM-F-1767 cultures grown under nitrogen-limited conditions. Cultures supplemented with 0.4 to 2 mM veratryl alcohol showed increased lignin peroxidase activity. Addition of veratryl alcohol had no effect on Mn-dependent peroxidase activity and inhibited glyoxal oxidase activity. Azure-casein analysis of acidic proteases in the extracellular fluid showed that protease activity decreased during the early stages of secondary metabolism while lignin peroxidase activity was at its peak, suggesting that proteolysis was not involved in the regulation of lignin peroxidase activity during early secondary metabolism. In cultures supplemented with lignin or veratryl alcohol, no induction of mRNA coding for lignin peroxidase H2 or H8 was observed. Veratryl alcohol protected lignin peroxidase isozymes H2 and H8 from inactivation by H2O2. We conclude that veratryl alcohol acts as a stabilizer of lignin peroxidase activity and not as an inducer of lignin peroxidase synthesis. 相似文献
9.
Doan Minh Sang Ik Ho Na Dr. Duong Tien Anh Do Thi Mai Dung Nguyen Thi Thu Hang Nguyen T. Phuong-Anh Assoc. Prof. Dr. Pham-The Hai Assoc. Prof. Dr. Dao Thi Kim Oanh Dr. Truong Thanh Tung Soo Jung Lee Joo Hee Kwon Prof. Dr. Jong Soon Kang Prof. Dr. Sang-Bae Han Assoc. Prof. Dr. Dinh Thi Thanh Hai Prof. Dr. Nguyen-Hai Nam 《化学与生物多样性》2023,20(5):e202201030
Herein, we report the design, synthesis and evaluation of novel (E)-3-(3-oxo-4-substituted-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-N-hydroxypropenamides ( 4 a – i , 7 a – g ) targeting histone deacetylases. Three human cancer cell lines were used to test the cytotoxicity of the synthesized compounds (SW620, colon; PC-3, prostate; NCI−H23, lung cancer); inhibitory activity towards HDAC; anticancer activity; as well as their impact on the cell cycle and apoptosis. As a result, compounds 4 a – i bearing the alkyl substituents seemed to be less potent than the benzyl-containing compounds 7 a – g in all biological assays. Compounds 7 e – f were found to be the most active HDAC inhibitors with IC50 of 1.498±0.020 μM and 1.794±0.159 μM, respectively. In terms of cytotoxicity and anticancer assay, 7 e and 7 f also showed good activity with IC50 values in the micromolar range. In addition, the cell cycle and apoptosis of SW620 were affected by compound 7 f in almost a similar manner to that of reference compound SAHA. Docking assays were carried out for analysis the binding mode and selectivity of this compound toward 8 HDAC isoforms. Overall, our data confirmed that the inhibition of HDAC plays a pivotal role in their anticancer activity. 相似文献
10.
Y. Yie Z. X. Wu S. Y. Wang S. Z. Zhao T. Q. Zhang G. Y. Yao P. Tien 《Transgenic research》1995,4(4):256-263
A procedure for the fast production of homozygotic transgenic plants was developed. Leaf discs of haploid tobacco plants from anther cultures were transformed with a chimaeric vector containing coat protein (CP) and satellite RNA (Sat-RNA) genes from cucumber mosaic virus (CMV). One-hundred-and-twelve Kanamycin-resistant transformed haploid plants were subjected to selection based on the expression of both CP and Sat-RNA. Eighty-nine transgenic plants expressing both genes were selected and tested for their resistance to CMV by inoculation with high concentration of CMV (200 g ml–1). Only five plants showed no symptoms of viral infection 30 days after inoculation. These plants were then diploidized by colchicine treatment. Three homozygous diploid lines with high levels of resistance to CMV were obtained after only one generation. The three transgenic lines were further tested under field conditions. The results showed that the progenies of these transgenic lines were homozygous and were highly resistant to CMV under natural field infection and manual inoculation conditions. 相似文献