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231.
Anthi Petrou Emine Terzi Ozen Ozensoy Guler Claudiu T. Supuran 《Journal of enzyme inhibition and medicinal chemistry》2016,31(6):1306-1311
Carbonic anhydrases (CAs, EC 4.2.1.1) catalyze the fundamental reaction of CO2 hydration in all living organisms, being actively involved in the regulation of a plethora of patho/physiological conditions. A series of benzothiazole-based sulfonamides were synthesized and tested as possible CA inhibitors. Their inhibitory activity was assessed against the cytosolic human isoforms hCA I and hCA II and the transmembrane hCA IX and hCA XII. Several of the investigated derivatives showed interesting inhibition activity and selectivities for inhibiting hCA IX and hCA XII over the off-target ones hCA I and hCA II. Furthermore, computational procedures were used to investigate the binding mode of this class of compounds, within the active site of hCA IX. 相似文献
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233.
Knaus EE Innocenti A Scozzafava A Supuran CT 《Bioorganic & medicinal chemistry letters》2011,21(19):5892-5896
A series of compounds incorporating regioisomeric phenylethynylbenzenesulfonamide moieties has been investigated for the inhibition of four human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms, hCA I, II, IX and XII. Inhibition between the low nanomolar to the milliomolar range has been observed against them, with several low nanomolar and tumor-CA selective inhibitors detected. The position of the sulfamoyl group with respect to the alkyne functionality, and the nature of the moieties substituting the second aromatic ring were the principal structural features influencing CA inhibition. The para-sulfamoyl-substituted derivatives were effective inhibitors of CA IX and XII, the meta-substituted regioisomers of CA I, IX and XII, whereas the ortho-substituted sulfonamides were weak inhibitors of CA I, II and IX, but inhibited significantly CA XII. 相似文献
234.
The structure and diversity, including seasonal variation, and the energy budget of the benthic fauna in southern Lake Manitoba were studied and related to physical and chemical properties of the water and sediment. A total of 47 taxa were identified but 90 percent of individuals were represented by seven taxa (Candona rawsoni, Cytheromorpha fuscata, Pisidium spp., Amnicola limosa, Harnischia curtilamellata, Procladius freemani and Chironomus sp.). The spatial and temporal dynamics, dispersion patterns and life cycles of these abundant species are described.The net production was 5.05 Kcal/m2/yr for the only carnivorous species (Procladius freemani) and 28.53 Kcal/m2/yr for non-carnivorous species. The gastropod Amnicola limosa and the chironomid Chironomus sp. appear to be the most important contributors to the total biomass and net production of the community. Annual turnover rate (P/B) for all seven taxa aver-aged 2.82, with the chironomid species having the highest value and the gastropod species the lowest (3.7 and 1.75 respectively).Contribution No. 52 of the University of Manitoba Field Station (Delta Marsh). 相似文献
235.
Claudia Temperini Alessandro Cecchi Andrea Scozzafava Claudiu T. Supuran 《Bioorganic & medicinal chemistry》2009,17(3):1214-1221
Thiazide and high ceiling diuretics were recently shown to inhibit all mammalian isoforms of carbonic anhydrase (CA, EC 4.2.1.1) with a very different profile as compared to classical inhibitors, such as acetazolamide, methazolamide, and ethoxzolamide. Some of these structurally related compounds have a very different behavior against the widespread isozyme CA II, with chlorthalidone, trichloromethiazide, and furosemide being efficient inhibitors against CA II (KIs of 65–138 nM), whereas indapamide is a much weaker one (KI of 2520 nM). Furthermore, some of these diuretics are quite efficient (low nanomolar) inhibitors of other isoforms, for example, chlorthalidone against hCA VB, VII, IX, and XIII; indapamide against CA VII, IX, XII, and XIII, trichloromethiazide against CA VII and IX, and furosemide against CA I and XIV. Examining the four X-ray crystal structures of their CA II adducts, we observed several (2–3) active site water molecules interacting with the chlorthalidone, trichloromethiazide, and furosemide scaffolds which may be responsible for this important difference of activity. Indeed, indapamide bound to CA II has no interactions with active site water molecules. Chlorthalidone bound within the CA II active site is in an enolic (lactimic) tautomeric form, with the enolic OH also participating in two strong hydrogen bonds with Asn67 and a water molecule. The newly evidenced binding modes of these diuretics may be exploited for designing better CA II inhibitors as well as compounds with selectivity/affinity for various isoforms with medicinal chemistry applications. 相似文献
236.
237.
Menchise V De Simone G Di Fiore A Scozzafava A Supuran CT 《Bioorganic & medicinal chemistry letters》2006,16(24):6204-6208
The X-ray crystal structures of 5-amino-1,3,4-thiadiazole-2-sulfonamide (the acetazolamide precursor) and 5-(4-amino-3-chloro-5-fluorophenylsulfonamido)-1,3,4-thiadiazole-2-sulfonamide in complex with the human isozyme II of carbonic anhydrase (CA, EC 4.2.1.1) are reported. The thiadiazole-sulfonamide moiety of the two compounds binds in the canonic manner to the zinc ion and interacts with Thr199, Glu106, and Thr200. The substituted phenyl tail of the second inhibitor was positioned in the hydrophobic part of the binding pocket, at van der Waals distance from Phe131, Val 135, Val141, Leu198, Pro202, and Leu204. These structures may help in the design of better inhibitors of these widespread zinc-containing enzymes. 相似文献
238.
239.
Two series of disubstituted coumarins incorporating ether and acetyl/propionyl moieties in positions 6,7- and 7,8- of the heterocyclic ring were synthesized investigated for the inhibition of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1). All these coumarins were very weak or ineffective as inhibitors of the housekeeping, offtarget isoforms CA I and II. The 6,7-disubstituted series showed ineffective inhibition also for the transmembrane tumor-associated isoforms CA IX and XII, whereas the corresponding isomeric 7,8-disubstituted coumarins showed nanomolar/subnanomolar inhibition of CA IX/XII. The nature and position of the groups substituting the coumarin ring in the 7,8-positions greatly influenced CA inhibitory properties, with C1-C4 alkyl ethers being the most effective inhibitors. 相似文献
240.
Anthony Bertucci Didier Zoccola Sylvie Tambutté Daniela Vullo Claudiu T. Supuran 《Bioorganic & medicinal chemistry》2010,18(6):2300-2303
The activity of the coral Stylophora pystillata secretory carbonic anhydrase STPCA has been tested in presence of amino acids and amines. All the investigated compounds showed a positive, activating effect on kcat and have been separated in weak (KA in the range of 21–126 μM), medium (10.1–19 μM) and strong enzyme activators (KA of 0.18–3.21 μM). D-DOPA was found to be the best coral enzyme activator, with an activation constant KA of 0.18 μM. This enhancement of STPCA activity, as well as previous enzyme inhibition results, might now be tested on living organisms to better understand the role played by these enzymes in the coral calcification processes. 相似文献