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81.
Miloš R. Filipović Dragana Stanić Smiljana Raičević Mihajlo Spasić 《Free radical research》2013,47(1):62-72
The present study demonstrates that manganese superoxide dismutase (MnSOD) (Escherichia coli), binds nitric oxide (√NO) and stimulates its decay under both anaerobic and aerobic conditions. The results indicate that previously observed MnSOD-catalyzed √NO disproportionation (dismutation) into nitrosonium (NO+) and nitroxyl (NO? ) species under anaerobic conditions is also operative in the presence of molecular oxygen. Upon sustained aerobic exposure to √NO, MnSOD-derived NO? species initiate the formation of peroxynitrite (ONOO? ) leading to enzyme tyrosine nitration, oxidation and (partial) inactivation. The results suggest that both ONOO? decomposition and ONOO? -dependent tyrosine residue nitration and oxidation are enhanced by metal centre-mediated catalysis. We show that the generation of ONOO? is accompanied by the formation of substantial amounts of H2O2. MnSOD is a critical mitochondrial antioxidant enzyme, which has been found to undergo tyrosine nitration and inactivation in various pathologies associated with the overproduction of √NO. The results of the present study can account for the molecular specificity of MnSOD nitration in vivo. The interaction of √NO with MnSOD may represent a novel mechanism by which MnSOD protects the cell from deleterious effects associated with overproduction of √NO. 相似文献
82.
A. Žákovská H. Nejezchlebová N. Bartoňková T. Rašovská H. Kučerová A. Norek P. Ovesná 《Journal of vector ecology》2013,38(2):295-300
The ever‐increasing number of Lyme borreliosis patients led us to consider more effective procedures for disease prevention. The aim of our study was to monitor the annual activity and infectivity of Ixodes ricinus ticks in the Pisárky region, City of Brno, CR, and to test the responses of the locally‐captured ticks to selected repellents. The result of regular one‐hour‐perweek monitoring in 2011 was the collection of ticks that directly reflected the highest number of Lyme disease patients (4,835) detected throughout the period of recording in the Czech Republic. The ticks were examined for spirochaetes by dark field microscopy. The positive samples were identified by PCR analysis, confirming that 76% of these were infected with Borrelia burgdorferi sensu lato. Ticks were most abundant in May and June, with August having the highest risk for spirochaetal infection. Tick activity was statistically correlated with temperature. The moving‐object‐bioassay was used to study repellent efficiency on the Ixodes ricinus nymphs captured in the above‐mentioned suburban park. Five selected commercial repellents based on DEET (N, N‐diethyl3methylbenzamide) showed statistically different effects on the non‐repellent control group. 相似文献
83.
Abstract Viscum album L. ssp. album is semi-parasitic on deciduous trees and shrubs. In order to identify hosts and map the distribution of V. album ssp. album in Croatia and Slovenia, field research was carried out, and herbaria were surveyed. In Croatia and Slovenia, V. album ssp. album occurred on 59 taxa. In Croatia, there were 52 hosts (33 autochthonous and 15 allochthonous species, two cultivars and two hybrids). In Slovenia, there were 25 hosts (21 autochthonous and four allochthonous species). There were 18 hosts common to both countries, 34 hosts were found only in Croatia, and seven hosts only in Slovenia. The hosts belonged to 13 families. The majority of these (19 species) belong to the Rosaceae, followed by Salicaceae, Aceraceae, Betulaceae, Fagaceae, Juglandaceae, Tiliaceae, Hippocastanaceae, Ulmaceae, Oleaceae, Fabaceae, Moraceae and Viscaceae. All hosts have been previously recorded in the literature, except Alnus japonica (Thunb.) Steud., Amelanchier lamarckii F.G. Schroed. and Crataegus nigra Waldst. et Kit. The distribution of this mistletoe was scattered, due to the scattered distribution of hosts, local conditions, movement of bird-vectors, etc. A continuous distribution was found only in part of the distribution area of narrow-leaved ash (Fraxinus angustifolia Vahl). 相似文献
84.
Robert Brus Dalibor Ballian Faruk Bogunić Martin Bobinac Marilena IdžOjtić 《Plant biosystems》2013,147(2):278-285
Abstract In most European countries, the service tree (Sorbus domestica L.) is a rare and threatened species and its conservation has been recognised as a priority. The aim of this study was to asses its morphologic variation in the western and central part of the Balkan Peninsula and in southern Central Europe. Three populations were analysed: one in Serbia, one in Bosnia and Herzegovina and one in Slovenia. In each population 30 trees were selected, and from each tree 30 leaves were collected for morphometric analysis based on nine leaflet morphological traits. Univariate (ANOVA) and multivariate (MANOVA) analysis of variance were used to estimate the variation within- and between populations and a discriminant analysis was performed to examine the structure of the between-population differences. The values of particular morphological traits found in our study did not differ considerably from the values reported elsewhere. The results revealed significant within- and between population variation. Variation within populations was highly significant for all the scored leaf morphological traits, while variation between populations was significant for all the studied traits except for the leaflet length. The discrimination between the three populations was significant. High percentages of correctly classified samples demonstrate good discriminating employability of the analysed leaf morphological traits and indicate differentiation of the analysed populations. 相似文献
85.
Danijela Krstić Katarina Krinulović Vesna Vasić 《Journal of enzyme inhibition and medicinal chemistry》2013,28(5):469-476
Kinetics and inhibition of Na+/K+-ATPase and Mg2+-ATPase activity from rat synaptic plasma membrane (SPM), by separate and simultaneous exposure to transition (Cu2+, Zn2+, Fe2+ and.Co2+) and heavy metals (Hg2+and Pb2+) ions were studied. All investigated metals produced a larger maximum inhibition of Na+/K+-ATPase than Mg2+-ATPase activity. The free concentrations of the key species (inhibitor, MgATP2 ? , MeATP2 ? ) in the medium assay were calculated and discussed. Simultaneous exposure to the combinations Cu2+/Fe2+ or Hg2+/Pb2+caused additive inhibition, while Cu2+/Zn2+ or Fe2+/Zn2+ inhibited Na+/K+-ATPase activity synergistically (i.e., greater than the sum metal-induced inhibition assayed separately). Simultaneous exposure to Cu2+/Fe2+ or Cu2+/Zn2+ inhibited Mg2+-ATPase activity synergistically, while Hg2+/Pb2+ or Fe2+/Zn2+ induced antagonistic inhibition of this enzyme. Kinetic analysis showed that all investigated metals inhibited Na+/K+-ATPase activity by reducing the maximum velocities (Vmax) rather than the apparent affinity (Km) for substrate MgATP2-, implying the noncompetitive nature of the inhibition. The incomplete inhibition of Mg2+-ATPase activity by Zn2+, Fe2+ and Co2+ as well as kinetic analysis indicated two distinct Mg2+-ATPase subtypes activated in the presence of low and high MgATP2 ? concentration. EDTA, L-cysteine and gluthathione (GSH) prevented metal ion-induced inhibition of Na+/K+-ATPase with various potencies. Furthermore, these ligands also reversed Na+/K+-ATPase activity inhibited by transition metals in a concentration-dependent manner, but a recovery effect by any ligand on Hg2+-induced inhibition was not obtained. 相似文献
86.
New inhibitors of fungal 17β-hydroxysteroid dehydrogenase based on the [1,5]-benzodiazepine scaffold
Matej Živec Matej Sova Mojca Brunskole Roman Lenaršič Tea Lanišnik Rižner Stanislav Gobec 《Journal of enzyme inhibition and medicinal chemistry》2013,28(1):29-36
The synthesis and activity of a new series of non-steroidal inhibitors of 17β-hydroxysteroid dehydrogenase that are based on a 1,5-benzodiazepine scaffold are presented. Their inhibitory potential was screened against 17β-hydroxysteroid dehydrogenase from the fungus Cochliobolus lunatus (17β-HSDcl), a model enzyme of the short-chain dehydrogenase/reductase superfamily. Some of these compounds are potent inhibitors of 17β-HSDcl activity, with IC50 values in the low micromolar range and represent promising lead compounds that should be further developed and investigated as inhibitors of human 17β-HSD isoforms, which are the enzymes associated with the development of many hormone-dependent and neuronal diseases. 相似文献
87.
Aleksandrs Pustenko Alessio Nocentini Anastasija Balašova Ahmed Alafeefy Mikhail Krasavin Raivis Žalubovskis 《Journal of enzyme inhibition and medicinal chemistry》2013,28(1):245-254
Abstract A new series of homosulfocoumarins (3H-1,2-benzoxathiepine 2,2-dioxides) possessing various substitution patterns and moieties in the 7, 8 or 9 position of the heterocylic ring were prepared by original procedures and investigated for the inhibition of four physiologically relevant carbonic anhydrase (CA, EC 4.2.1.1) isoforms, the human (h) hCA I, II, IX and XII. The 8-substituted homosulfocoumarins were the most effective hCA IX/XII inhibitors followed by the 7-substituted derivatives, whereas the substitution pattern in position 9 led to less effective binders for the transmembrane, tumour-associated isoforms IX/XII. The cytosolic isoforms hCA I and II were not inhibited by these compounds, similar to the sulfocoumarins/coumarins investigated earlier. As hCA IX and XII are validated anti-tumour targets, with one sulphonamide (SLC-0111) in Phase Ib/II clinical trials, finding derivatives with better selectivity for inhibiting the tumour-associated isoforms over the cytosolic ones, as the homosulfocoumarins reported here, is of crucial importance. 相似文献
88.
Ivana Šagud Nikolina Maček Hrvat Ana Grgičević Tena Čadež Josipa Hodak Milena Dragojević 《Journal of enzyme inhibition and medicinal chemistry》2013,28(1):460-467
Abstract The enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are primary targets in attenuating the symptoms of neurodegenerative diseases. Their inhibition results in elevated concentrations of the neurotransmitter acetylcholine which supports communication among nerve cells. It was previously shown for trans-4/5-arylethenyloxazole compounds to have moderate AChE and BChE inhibitory properties. A preliminary docking study showed that elongating oxazole molecules and adding a new NH group could make them more prone to bind to the active site of both enzymes. Therefore, new trans-amino-4-/5-arylethenyl-oxazoles were designed and synthesised by the Buchwald-Hartwig amination of a previously synthesised trans-chloro-arylethenyloxazole derivative. Additionally, naphthoxazole benzylamine photoproducts were obtained by efficient photochemical electrocyclization reaction. Novel compounds were tested as inhibitors of both AChE and BChE. All of the compounds exhibited binding preference for BChE over AChE, especially for trans-amino-4-/5-arylethenyl-oxazole derivatives which inhibited BChE potently (IC50 in µM range) and AChE poorly (IC50?100?µM). Therefore, due to the selectivity of all of the tested compounds for binding to BChE, these compounds could be applied for further development of cholinesterase selective inhibitors.
- HIGHLIGHTS
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Series of oxazole benzylamines were designed and synthesised
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The tested compounds showed binding selectivity for BChE
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Naphthoxazoles were more potent AChE inhibitors
89.
Mikhail Krasavin Raivis Žalubovskis Aiga Grandāne Ilona Domračeva Petr Zhmurov 《Journal of enzyme inhibition and medicinal chemistry》2013,28(1):506-510
Abstract The hypothesis that sulfocoumarin acting as inhibitors of human carbonic anhydrase (CA, EC 4.2.1.1) cancer-associated isoforms hCA IX and – hCA XII is being able to also inhibit thioredoxin reductase was verified and confirmed. The dual targeting of two cancer cell defence mechanisms, i.e. hypoxia and oxidative stress, may both contribute to the observed antiproliferative profile of these compounds against many cancer cell lines. This unprecedented dual anticancer mechanism may lead to a new approach for designing innovative therapeutic agents. 相似文献
90.
S. Raić M. Pongraćić J. Vorkapić-Furać D. Vikić-Topić A. Hergold-Brundić A. Nagl 《Nucleosides, nucleotides & nucleic acids》2013,32(4):937-960
Abstract Synthesis of the novel nucleoside analogues containing exocyclic pyrrolo moiety and acyclic side chains attached to the purine ring at N-9 and N-7 is described. The site of alkylation was determined by 1H and 13C NMR on the basis of chemical shifts, C-H coupling constants and connectivity in NOESY and HETCOR spectra. The N-9 substitution of 7 was proved by its X-ray crystallographic analysis. 相似文献