全文获取类型
收费全文 | 522篇 |
免费 | 3篇 |
出版年
2023年 | 1篇 |
2022年 | 11篇 |
2021年 | 26篇 |
2019年 | 4篇 |
2018年 | 8篇 |
2017年 | 13篇 |
2016年 | 25篇 |
2015年 | 5篇 |
2014年 | 5篇 |
2013年 | 81篇 |
2012年 | 27篇 |
2011年 | 32篇 |
2010年 | 31篇 |
2009年 | 44篇 |
2008年 | 34篇 |
2007年 | 30篇 |
2006年 | 25篇 |
2005年 | 41篇 |
2004年 | 40篇 |
2003年 | 19篇 |
2002年 | 13篇 |
1999年 | 1篇 |
1997年 | 1篇 |
1992年 | 1篇 |
1990年 | 1篇 |
1989年 | 2篇 |
1988年 | 1篇 |
1983年 | 1篇 |
1979年 | 1篇 |
1972年 | 1篇 |
排序方式: 共有525条查询结果,搜索用时 156 毫秒
31.
Chohan ZH Scozzafava A Supuran CT 《Journal of enzyme inhibition and medicinal chemistry》2002,17(4):261-266
Condensation reactions of 1,1'-diacetylferrocene with different heteroaromatic amines such as, 2-amino-1,3,4-thiadiazole, 5-aminotetrazole and 3-amino-1,2,4-triazole to form unsymmetrically 1,1'-disubstituted ferrocenes have been studied. The obtained compounds have been further investigated for their liganding and biological properties upon chelation with Co(II), Cu(II), Ni(II) and Zn(II) metal ions. The synthesized compounds have been characterized by physical, spectral and analytical data and have been screened against pathogenic bacterial strains e.g., Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus, showing moderate activity as antibacterials in vitro. 相似文献
32.
Chohan ZH Iqbal MS Iqbal HS Scozzafava A Supuran CT 《Journal of enzyme inhibition and medicinal chemistry》2002,17(2):87-91
Mononuclear and binuclear transition metal [Co(II), Cu(II), Ni(II) and Zn(II)] acetylsalicylates of the type [M(L)2], [M(L)2Cl2] and [(M)2(L)4] have been prepared and characterized on the basis of their physical, spectral and analytical data. The complexes have been investigated in an in vivo animal model for anti-inflammatory activity and show a better effect and a more potent action than acetylsalicylic acid. 相似文献
33.
Franchi M Vullo D Gallori E Pastorek J Russo A Scozzafava A Pastorekova S Supuran CT 《Journal of enzyme inhibition and medicinal chemistry》2003,18(4):333-338
A series of new compounds was obtained by reaction of aromatic/heterocyclic sulfonamides incorporating amino groups with N,N-diphenylcarbamoyl chloride and diphenylacetyl chloride. These sulfonamides were assayed for the inhibition of three carbonic anhydrase (CA, EC 4.2.1.1) isozymes: the cytosolic CA I and CA II, and the transmembrane, cancer-associated isozyme CA IX. Good inhibitors against all these isoforms were detected, and the inhibition profile of the newly investigated isozyme IX was observed to be different from that of the cytosolic isozymes, I and II. This may lead to the development of novel anticancer therapies based on the selective inhibition of CA IX. 相似文献
34.
Santos MA Marques S Gil M Tegoni M Scozzafava A Supuran CT 《Journal of enzyme inhibition and medicinal chemistry》2003,18(3):233-242
A series of succinyl hydroxamates/bishydroxamates as well as a new structural type of matrix metalloproteinase (MMP)/bacterial protease (BP) inhibitors, incorporating iminodiacetic (IDA) hydroxamate/bishydroxamate moieties, has been synthesized and tested for interaction with four vertebrate proteases, MMP-1, MMP-2, MMP-8 and MMP-9, and a BP, the collagenase isolated from Clostridium histolyticum (ChC). The new derivatives generally showed inhibition constants in the range of 8-62 nM against the five proteases mentioned above. 相似文献
35.
Samer Al-Samir Maximilian Prill Claudiu T. Supuran Gerolf Gros Volker Endeward 《Journal of enzyme inhibition and medicinal chemistry》2021,36(1):1602
We have studied the CO2 permeability of the erythrocyte membrane of the rat using a mass spectrometric method that employs 18 O-labelled CO2. The method yields, in addition, the intraerythrocytic carbonic anhydrase activity and the membrane HCO3− permeability. For normal rat erythrocytes, we find at 37 °C a CO2 permeability of 0.078 ± 0.015 cm/s, an intracellular carbonic anhydrase activity of 64,100, and a bicarbonate permeability of 2.1 × 10−3 cm/s. We studied whether the rat erythrocyte membrane possesses protein CO2 channels similar to the human red cell membrane by applying the potential CO2 channel inhibitors pCMBS, Dibac, phloretin, and DIDS. Phloretin and DIDS were able to reduce the CO2 permeability by up to 50%. Since these effects cannot be attributed to the lipid part of the membrane, we conclude that the rat erythrocyte membrane is equipped with protein CO2 channels that are responsible for at least 50% of its CO2 permeability. 相似文献
36.
Alessio Innocenti Ilhami Gülçin Andrea Scozzafava Claudiu T. Supuran 《Bioorganic & medicinal chemistry letters》2010,20(17):5050-5053
A series of polyphenolic derivatives, including resveratrol, dobutamine, curcumin, catechin and silymarine were investigated for the inhibition of all the catalytically active mammalian isozymes of the metalloprotein carbonic anhydrase (CA, EC 4.2.1.1), that is, CA I–CA XV. These polyphenols effectively inhibited CAs, with KIs in the range of 380 nM–12.02 μM. The various isozymes showed quite diverse inhibition profiles with these compounds, which possess scaffolds not present in other investigated CA inhibitors (CAIs). These data may lead to drug design campaigns of effective CAIs possessing a diverse inhibition mechanism compared to sulfonamide/sulfamate inhibitors, based on such less investigated scaffolds. 相似文献
37.
38.
39.
Carbonic anhydrase IX: Biochemical and crystallographic characterization of a novel antitumor target
Giuseppina De Simone Claudiu T. Supuran 《Biochimica et Biophysica Acta - Proteins and Proteomics》2010,1804(2):404-409
Isoform IX of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1), CA IX, is a transmembrane protein involved in solid tumor acidification through the HIF-1α activation cascade. CA IX has a very high catalytic activity for the hydration of carbon dioxide to bicarbonate and protons, even at acidic pH values (of around 6.5), typical of solid, hypoxic tumors, which are largely unresponsive to classical chemo- and radiotherapy. Thus, CA IX is used as a marker of tumor hypoxia and as a prognostic factor for many human cancers. CA IX is involved in tumorigenesis through many pathways, such as pH regulation and cell adhesion control. The X-ray structure of the catalytic domain of CA IX has been recently reported, being shown that CA IX has a typical α-CA fold. However, the CA IX structure differs significantly from the other CA isozymes when the protein quaternary structure is considered. Thus, two catalytic domains of CA IX associate to form a dimer, which is stabilized by the formation of an intermolecular disulfide bond. The active site clefts and the proteoglycan (PG) domains are located on one face of the dimer, while the C-termini are located on the opposite face to facilitate protein anchoring to the cell membrane. As all mammalian CAs, CA IX is inhibited by several main classes of inhibitors, such as the inorganic anions, the sulfonamides and their bioisosteres (sulfamates, sulfamides, etc.), the phenols, and the coumarins. The mechanism of inhibition with all these classes of compounds is understood at the molecular level, but the sulfonamides and their congeners have important applications. It has been recently shown that both in vitro, in cell cultures, as well as in animals with transplanted tumors, CA IX inhibition with sulfonamides lead to a return of the extracellular pH to more normal values, which leads to a delay in tumor growth. As a consequence, CA IX represents a promising antitumor target for the development of anticancer agents with an alternative mechanism of action. 相似文献
40.
Temperini C Winum JY Montero JL Scozzafava A Supuran CT 《Bioorganic & medicinal chemistry letters》2007,17(10):2795-2801
N-Hydroxysulfamide is a 2000-fold more potent inhibitor of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1) as compared to sulfamide. It also inhibits other physiologically relevant isoforms, such as the tumor-associated CA IX and XII (K(I)s in the range of 0.865-1.34microM). In order to understand the binding of this inhibitor to the enzyme active site, the X-ray crystal structure of the human hCA II-N-hydroxysulfamide adduct was resolved. The inhibitor coordinates to the active site zinc ion by the ionized primary amino group, participating in an extended network of hydrogen bonds with amino acid residues Thr199, Thr200 and two water molecules. The additional two hydrogen bonds in which N-hydroxysulfamide bound to hCA II is involved as compared to the corresponding adduct of sulfamide may explain its higher affinity for the enzyme, also providing hints for the design of tight-binding CA inhibitors possessing an organic moiety substituting the NH group in the N-hydroxysulfamide structure. 相似文献