全文获取类型
收费全文 | 5639篇 |
免费 | 369篇 |
国内免费 | 3篇 |
出版年
2024年 | 7篇 |
2023年 | 30篇 |
2022年 | 81篇 |
2021年 | 121篇 |
2020年 | 90篇 |
2019年 | 112篇 |
2018年 | 163篇 |
2017年 | 127篇 |
2016年 | 230篇 |
2015年 | 342篇 |
2014年 | 371篇 |
2013年 | 425篇 |
2012年 | 506篇 |
2011年 | 510篇 |
2010年 | 346篇 |
2009年 | 288篇 |
2008年 | 402篇 |
2007年 | 337篇 |
2006年 | 310篇 |
2005年 | 257篇 |
2004年 | 262篇 |
2003年 | 221篇 |
2002年 | 173篇 |
2001年 | 50篇 |
2000年 | 43篇 |
1999年 | 38篇 |
1998年 | 34篇 |
1997年 | 23篇 |
1996年 | 24篇 |
1995年 | 15篇 |
1994年 | 12篇 |
1993年 | 5篇 |
1992年 | 8篇 |
1991年 | 4篇 |
1990年 | 5篇 |
1989年 | 4篇 |
1988年 | 4篇 |
1986年 | 2篇 |
1985年 | 4篇 |
1983年 | 3篇 |
1982年 | 3篇 |
1981年 | 2篇 |
1976年 | 2篇 |
1975年 | 2篇 |
1974年 | 2篇 |
1973年 | 2篇 |
1971年 | 1篇 |
1967年 | 1篇 |
1965年 | 2篇 |
1962年 | 1篇 |
排序方式: 共有6011条查询结果,搜索用时 31 毫秒
11.
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
12.
Ayoub Kdimy Dr. Seong Jong Kim Dr. Zulfiqar Ali Dr. Md Imdadul H. Khan Dr. Siddharth K. Tripathi Prof. Souad El Hajjaji Prof. Hoang V. Le 《化学与生物多样性》2023,20(9):e202300903
Many plants have been known to be contaminated and accumulate plasticizers from the environment, including water sources, soil, and atmosphere. Plasticizers are used to confer elasticity and flexibility to various fiber and plastic products. Consumption of plasticizers can lead to many adverse effects on human health, including reproductive and developmental toxicity, endocrine disruption, and cancer. Herein, we report for the first time that two plasticizers, bis(2-ethylhexyl) terephthalate (DEHT) and bis(2-ethylhexyl) phthalate (DEHP), have been isolated from the leaves of Capparis spinosa L. (the caper bush), a plant that is widely used in food seasonings and traditional medicine. 297 mg/kg of DEHT and 48 mg/kg of DEHP were isolated from dried and grounded C. spinosa L. leaves using column chromatography and semi-preparative high-performance liquid chromatography. Our study adds to the increase in the detection of plasticizers in our food and medicinal plants and to the alarming concern about their potential adverse effects on human health. 相似文献
13.
14.
The polyamine-derived amino acid hypusine: its post-translational formation in eIF-5A and its role in cell proliferation 总被引:1,自引:0,他引:1
Myung Hee Park Young Ae Joe Kee Ryeon Kang Young Bok Lee Edith C. Wolff 《Amino acids》1996,10(2):109-121
Summary The unusual amino acid hypusine [N
-(4-amino-2-hydroxybutyl)lysine] is a unique component of one cellular protein, eukaryotic translation initiation factor 5A (eIF-5A, old terminology, eIF-4D). It is formed posttranslationally and exclusively in this protein in two consecutive enzymatic reactions, (i) modification of a single lysine residue of the eIF-5A precursor protein by the transfer of the 4-aminobutyl moiety of the polyamine spermidine to its-amino group to form the intermediate, deoxyhypusine [N
-(4-aminobutyl)lysine] and (ii) subsequent hydroxylation of this intermediate to form hypusine. The amino acid sequences surrounding the hypusine residue are strictly conserved in all eukaryotic species examined, suggesting the fundamental importance of this amino acid throughout evolution. Hypusine is required for the activity of eIF-5Ain vitro. There is strong evidence that hypusine and eIF-5A are vital for eukaryotic cell proliferation. Inactivation of both of the eIF-5A genes is lethal in yeast and the hypusine modification appears to be a requirement for yeast survival (Schnier et al., 1991 [Mol Cell Biol 11: 3105–3114]; Wöhl et al., 1993 [Mol Gen Genet 241: 305–311]). Furthermore, inhibitors of either of the hypusine biosynthetic enzymes, deoxyhypusine synthase or deoxyhypusine hydroxylase, exert strong anti-proliferative effects in mammalian cells, including many human cancer cell lines. These inhibitors hold potential as a new class of anticancer agents, targeting one specific eukaryotic cellular reaction, hypusine biosynthesis. 相似文献
15.
Internal pH crisis, lysine decarboxylase and the acid tolerance response of Salmonella typhimurium 总被引:10,自引:3,他引:7
Yong-Keun Park Bradley Bearson Seong Ho Bang Iel Soo Bang & John W. Foster 《Molecular microbiology》1996,20(3):605-611
Salmonella typhimurium possesses an adaptive response to acid that increases survival during exposure to extremely low pH values. The acid tolerance response (ATR) includes both log-phase and stationary-phase systems. The log-phase ATR appears to require two components for maximum acid tolerance, namely an inducible pH homeostasis system, and a series of acid-shock proteins. We have discovered one of what appears to be a series of inducible exigency pH homeostasis systems that contribute to acid tolerance in extreme acid environments. The low pH-inducible lysine decarboxylase was shown to contribute significantly to pH homeostasis in environments as low as pH 3.0. Under the conditions tested, both lysine decarboxylase and σs -dependent acid-shock proteins were required for acid tolerance but only lysine decarboxylase contributed to pH homeostasis. The cadBA operon encoding lysine decarboxylase and a lysine/cadaverine antiporter were cloned from S. typhimurium and were found to be 79% homologous to the cadBA operon from Escherichia coli . The results suggest that S. typhimurium has a variety of means of fulfilling the pH homeostasis requirement of the ATR in the form of inducible amino acid decarboxylases. 相似文献
16.
Hee Wook Ryu Kyung Suk Cho Young Keun Chang Ho Nam Chang 《Biotechnology Techniques》1996,10(12):899-904
Summary
Alcaligenes eutrophus was successfully recovered from high cell density broths by pre-treatment with polyaluminium hydroxide chloride silicate as a coagulant at 36–90 mg Al/l. The optimum pH range for cell coagulation was 10–12. Subsequent centrifugation (45×g) and filtration (pore size 0.5 mm) gave a cell recovery of higher than 90%. The energy demand for cell recovery with the coagulant was only 3–11% of that without it. 相似文献
17.
Summary Double fluorescent labeling, with fluorescein isothiocyanate (FITC)-labeled F(ab)2 specific for the heavy chain and R-phycoerythrin (R-PE)-labeled F(ab)2 specific for the light chain, was demonstrated as a convenient means for the accurate evaluation of a heterogeneous non-antibody-producing population. Furthermore, it could be used for monitoring the changes in each immunoglobulin (Ig) chain content of the cells during the batch culture, which will facilitate the study on antibody synthesis, assembly and secretion. 相似文献
18.
Summary In the production of L-cysteine from D,L-ATC stability of the relevant enzymes produced byPseudomonas sp. was tested, and strategies to improve the stability of L-ATC hydrolase were investigated in view of water activity and ionic strength. Among the three enzymes which participate in L-cysteine production, i.e., ATC racemase, L-ATC hydrolase, and S-carbamyl-L-cysteine hydrolase, L-ATC hydrolase is the least stable. Various mixtures of salts and sorbitol were added to adjust the water activities of the tested solutions. As water activity decreased from 0.93 to 0.80, the stability of L-ATC hydrolase was sharply enhanced. In the absence of sorbitol the stability of L-ATC hydrolase increased in proportion to ionic strength. Even though enzyme stability was not good at a low ionic strength, it was enhanced by lowering water activity with addition of sorbitol. The half life of L-ATC hydrolase in sorbitol-salt mixtures increased by tenfold to twentyfold compared to that of a control. 相似文献
19.
Identification of three genetic loci controlling leaf senescence in Arabidopsis thaliana 总被引:23,自引:3,他引:20
Sung Aeong Oh Joon-Hyun Park Gyu In Lee Kyung Hee Paek Soon Ki Park Hong Gil Nam 《The Plant journal : for cell and molecular biology》1997,12(3):527-535
Four mutants that show the delayed leaf senescence phenotype were isolated from Arabidopsis thaliana . Genetic analyses revealed that they are all monogenic recessive mutations and fall into three complementation groups, identifying three genetic loci controlling leaf senescence in Arabidopsis . Mutations in these loci cause delay in all senescence parameters examined, including chlorophyll content, photochemical efficiency of photosystem II, relative amount of the large subunit of Rubisco, and RNase and peroxidase activity. Delay of the senescence symptoms was observed during both age-dependent in planta senescence and dark-induced artificial senescence in all of the mutant plants. The results indicate that the three genes defined by the mutations are key genetic elements controlling functional leaf senescence and provide decisive genetic evidence that leaf senescence is a genetically programmed phenomenon controlled by several monogenic loci in Arabidopsis . The results further suggest that the three genes function at a common step of age-dependent and dark-induced senescence processes. It is further shown that one of the mutations is allelic to ein2-1 , an ethylene-insensitive mutation, confirming the role of ethylene signal transduction pathway in leaf senescence of Arabidopsis . 相似文献
20.
Callus cultures and cell suspension cultures derived from Ginkgo biloba L. leaves produced ginkgolidc B. In cell suspension cultures, the production reached a maximum by the 13th day of subculture and followed by a sharp decrease. The medium of Murashige and Skoog induced the highest ginkgolide B content in cultures while the medium of Schenk and Hildebrandt promoted cell growth. For the maximal production of ginkgolide B, cells were cultured in Murashige and Skoog medium modified to contain 1.0 mg/l of -naphthaleneacetic acid, 0.1 mg/1 of kinetin, 30 g/1 sucrose and 1.25 mM potassium phosphate with a molar ratio of ammonium to nitrate ions of 1 3.Abbreviations B5
Gamborg et al (1968) medium
- GKB
Ginkgolide B
- MS
Murashige and Skoog (1962) medium
- NAA
-naphthaleneacetic aicd
- SH
Schenk and Hildebrandt (1972) medium 相似文献