全文获取类型
收费全文 | 971篇 |
免费 | 49篇 |
国内免费 | 27篇 |
出版年
2023年 | 13篇 |
2022年 | 16篇 |
2021年 | 17篇 |
2020年 | 24篇 |
2019年 | 20篇 |
2018年 | 32篇 |
2017年 | 28篇 |
2016年 | 24篇 |
2015年 | 25篇 |
2014年 | 39篇 |
2013年 | 88篇 |
2012年 | 16篇 |
2011年 | 48篇 |
2010年 | 24篇 |
2009年 | 33篇 |
2008年 | 40篇 |
2007年 | 41篇 |
2006年 | 26篇 |
2005年 | 19篇 |
2004年 | 24篇 |
2003年 | 22篇 |
2002年 | 21篇 |
2001年 | 19篇 |
2000年 | 9篇 |
1999年 | 27篇 |
1998年 | 13篇 |
1997年 | 25篇 |
1996年 | 11篇 |
1995年 | 6篇 |
1994年 | 4篇 |
1993年 | 5篇 |
1992年 | 3篇 |
1991年 | 9篇 |
1990年 | 3篇 |
1989年 | 10篇 |
1988年 | 9篇 |
1987年 | 3篇 |
1986年 | 3篇 |
1985年 | 29篇 |
1984年 | 19篇 |
1983年 | 25篇 |
1982年 | 42篇 |
1981年 | 40篇 |
1980年 | 30篇 |
1979年 | 23篇 |
1978年 | 10篇 |
1977年 | 12篇 |
1976年 | 5篇 |
1974年 | 4篇 |
1973年 | 6篇 |
排序方式: 共有1047条查询结果,搜索用时 78 毫秒
31.
Ferdinand Bohlmann Jürgen Ziesche Robert M. King Harold Robinson 《Phytochemistry》1980,19(12):2675-2679
The investigation of two further Senecio species and the re-investigation of S. inaequidens afforded, in addition to known compounds, seven new furanoeremophilane derivatives. Six of these are closely related to cacalol, a sesquiterpene type which predominates in the species investigated. 相似文献
32.
Ferdinand Bohlmann Christa Zdero Robert M. King Harold Robinson 《Phytochemistry》1980,19(12):2663-2668
The investigation of three Eremanthus species afforded, in addition to known compounds, several new sesquiterpenelactones, a cumambrin B isobutyrate, four lactones related to the eremantholides, two to zexbrevin and one to goyazensolide. Furthermore, a new coniferyl alcohol derivative was isolated. The overall picture of the genus is very uniform. The occurrence of eremanthine and germacranolides with a furanone ring seems to be especially typical. 相似文献
33.
Kinetics of drug-DNA interaction. Dependence of the binding mechanism on structure of the ligand 总被引:2,自引:0,他引:2
Kinetic and equilibrium studies of the binding of several phenanthridines and acridines to DNA have been performed to investigate the physical processes underlying the direct ligand transfer mechanism of drug-DNA interaction· Substitution of the 6-phenyl ring of dimidium with a p-carboxyl residue, or complete removal of either the 6-substituent or the 3-amino group, does not prevent the phenanthridine chromophore from transferring directly between binding sites. Loss of the aromatic ring increases association rate constants three- to ninefold and enhances dissociation rates by factors of up to 12; the rates of direct transfer and dissociation from site 1 are the most perturbed. The presence of a phenyl ring stabilizes the site 1 complex and lowers the binding constant to site 2. Introduction of the p-carboxyl group does not affect the equilibrium distribution of bound forms but produces equivalent increases (2·5-fold) in forward and reverse rate constants for binding to site 1 and for the direct transfer step. The 3-amino group greatly stabilizes the site 1 complex. Its removal accelerates all kinetic processes except for the reverse transfer step; the transfer rate is enhanced 25-fold and binding to site 2 is increased 12-fold. The dissociation rate from site 1 rises by a factor of 45 and that from site 2 by a factor of 5·8.10-Methyl-9-aminoacridine binds via the direct transfer pathway with rate and equilibrium constants similar to those of the 3-desamino derivative of ethidium. This compound provides the first fully characterized example of an acridine that utilizes bimolecular transfer. By contrast, rivanol (6,9-diamino-2-ethoxyacridine) interacts with DNA via a two-step sequential mechanism analogous to that seen with proflavine, yet its intrinsic association constant is three times higher. This results from tighter ‘external’ attachment to the helix, together with a decrease in equilibrium constant for the insertion step, which is markedly slower than that of proflavine. There appears to be a simple relation between the apparent enthalpy of binding and the number of extracyclic amino substituents on the intercalating chromophore.We propose that the two bound forms that participate in direct ligand transfer represent molecules intercalated via one or other of the grooves of DNA, and that the transfer pathway corresponds to exchange of drug between the wide groove of one helix and the narrow groove of another. The ability to form strongly bound complexes at the surface of the helix appears to play a major role in determining the mechanism of ligand binding. 相似文献
34.
Ferdinand Bohlmann Rajinder K. Gupta Jasmin Jakupovic Harold Robinson Robert M. King 《Phytochemistry》1981,20(7):1609-1612
The re-investigation of Eremanthus glomerulatus afforded three new germacranolides and a guaianolide, while from E. mollis two known furanoheliangolides and a new phenylpropanol derivative were isolated. The germacranolides most probably are precursors of the widespread glaucolides. The structures were elucidated by spectroscopic methods. The chemotaxonomic situation is discussed briefly. 相似文献
35.
The investigation of Pegolettia senegalensis afforded several new sesquiterpene lactones, eight cis-6,12-germacra-trans,trans-1(10),4,11-trienolides, five cis-6,12-eudesmanolides, two elemanolides, 8,14-cyclogermacra-1(10),4,7(11)-trien-6,12-olide with a new carbon skeleton, three germacra-1(10),4,11(13)-trien-12-oic acids with ester residues at C-8, 18-hydroxygeranyl nerol, 1,3-dihydroxyoctadecane and a mixture of esters of 3,4-dihydroxy-dihydrocinnamyl alcohol. The structures were elucidated by high field 1HNMR spectroscopy and some chemical transformations. The C-10 configuration of 6,12-cis-eudesmanolides from Calostephane divaricata and Inula crithmoides most likely has to be corrected. The chemotaxonomic situation of the genus Pegolettia and biogenetic considerations are discussed briefly. 相似文献
36.
Reiko Nishino Shohei Hamada Elghareeb E. Elboray Yoshihiro Ueda Takeo Kawabata Takumi Furuta 《Chirality》2020,32(5):588-593
Axial chirality in N,N-dimethylaminopyridines as well as N,N-dipropylaminopyridines bearing an internal carboxy group were evaluated based on their racemization barriers and circular dichroism spectra. The half-life of racemization of N,N-dipropylaminopyridine derivative 2 was estimated to be 19.7 days at 20°C. Its enantiomers isolated as optically active forms showed positive-negative and negative-positive Cotton effects for (+)- 2 and (−)- 2 , respectively, from 310 to 210 nm. Furthermore, (−)- 2 was applied as a chiral nucleophilic catalyst and exhibited asymmetric induction in acylative kinetic resolution of 1-(1-naphthyl)ethane-1-ol. 相似文献
37.
《Bioorganic & medicinal chemistry letters》2020,30(11):127159
Indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO) are promising drug development targets due to their implications in pathologies such as cancer and neurodegenerative diseases. The search for IDO1 inhibitor has been intensely pursued but there is a paucity of potent TDO and IDO1/TDO dual inhibitors. Natural product tryptanthrin has been confirmed to bear IDO1 and/or TDO inhibitory activities. Herein, twelve novel tryptanthrin derivatives were synthesized and evaluated for the IDO1 and TDO inhibitory potency. All of the compounds were found to be IDO1/TDO dual inhibitors, in particular, compound 9a and 9b bore IDO1 inhibitory activity similar to that of INCB024360, and compound 5a and 9b had remarkable TDO inhibitory activity superior to that of the well-known TDO inhibitor LM10. This work enriches the collection of IDO1/TDO dual inhibitors and provides chemical molecules for potential development into drugs. 相似文献
38.
《Journal of enzyme inhibition and medicinal chemistry》2013,28(6):1010-1012
AbstractWe investigated a series of N-hydroxysulfamides obtained by Ferrier sulfamidoglycosylation for the inhibition of two bacterial carbonic anhydrases (CAs, EC 4.2.1.1) present in the pathogen Brucella suis. bsCA I was moderately inhibited by these compounds with inhibition constants ranging between 522 and 958?nM and no notable differences of activity between the acetylated or the corresponding deacetylated derivatives. The compounds incorporating two trans-acetates and the corresponding deprotected ones were the most effective inhibitors in the series. bsCA II was better inhibited, with inhibition constants ranging between 59.8 and 799?nM. The acetylated derivatives were generally better bsCA II inhibitors compared to the corresponding deacetylated compounds. Although these compounds were not highly isoform-selective CA inhibitors (CAIs) for the bacterial over the human CA isoforms, some of them possess inhibition profiles that make them interesting leads for obtaining better and more isoform-selective CAIs targeting bacterial enzymes. 相似文献
39.
Chang Hyun Oh Lian Jin Liu Joon Hee Hong 《Nucleosides, nucleotides & nucleic acids》2013,32(10):721-733
A novel 3′,4′-dimethyl-5′-norcarbocyclic adenosine phosphonic acid was prepared using acyclic stereoselective route from 4-hydroxybutan-2-one (4). To improve the cellular permeability and enhance the anti-HIV activity of this phosphonic acid, a (bis)SATE phosphonodiester nucleoside prodrug (20) was prepared and its chemical stability was evaluated. The newly synthesized bis(SATE) analogue (20) and its parent nucleoside phosphonic acid (18) were assayed for anti-HIV activity using an in vitro assay system in a CEM cell line. 相似文献
40.
Mohamed F. Abdel-Megeed Mohamed A. Saleh Youssef L. Aly Ibrahim M. Abdo 《Nucleosides, nucleotides & nucleic acids》2013,32(9-10):1985-1996
Abstract A series of some new acetylated S-glycosides of 2-thioxoquinazolin-4-ones, their thiono analogues and 3,1-benzothazin-2,4-dithione derivatives, including a D-glucose and a D-galactose derivatives and a D-xylose, and an L-arabinose derivatives have been synthesized. The conformation and configuration of these carbohydrate derivatives were determined by analysing their 1H and 13C NMR chemical shifts and coupling constants. The biological activity of these compounds has been studied. 相似文献