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Orain D Ofner S Koller M Carcache DA Froestl W Allgeier H Rasetti V Nozulak J Mattes H Soldermann N Floersheim P Desrayaud S Kallen J Lingenhoehl K Urwyler S 《Bioorganic & medicinal chemistry letters》2012,22(2):996-999
A new set of quinazolinedione sulfonamide derivatives as competitive AMPA receptor antagonist with improved properties compared to 1 is disclosed. By modulating physico-chemical properties, compound 29 was identified with a low ED(50) of 5.5mg/kg in an animal model of anticonvulsant activity after oral dosage. 相似文献
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González JF Degrassi G Devescovi G De Vleesschauwer D Höfte M Myers MP Venturi V 《Journal of Proteomics》2012,75(18):5911-5919
Xanthomonas oryzae pv. oryzae (Xoo) is the second most important rice pathogen, causing a disease called bacterial leaf blight. Xoo colonizes and infects the vascular tissue resulting in tissue necrosis and wilting causing significant yield losses worldwide. In this study Xoo infected vascular fluid (xylem sap) was recovered and analyzed for secreted Xoo proteins. Three independent experiments resulted in the identification of 324 different proteins, 64 proteins were found in all three samples which included many of the known virulence-associated factors. In addition, 10 genes encoding for the identified proteins were inactivated and one mutant displayed statistically a significant loss in virulence when compared to the wild type Xoo, suggesting that a new virulence-associated factor has been revealed. The usefulness of this approach in understanding the lifestyle and unraveling the virulence-associated factors of phytopathogenic vascular bacteria is discussed. 相似文献
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Giuliana Magnacca Enzo Laurenti Erika Vigna Flavia Franzoso Lorenzo Tomasso Enzo Montoneri Vittorio Boffa 《Process Biochemistry》2012,47(12):2025-2031
A silica monolith was prepared from commercial silica powder dispersed in water containing polymeric water soluble bio-organics (SBOs) isolated from composted urban vegetable wastes. The monolith and the pristine powder were characterized for their morphology and reactivity for immobilizing soybean peroxidase (SBP). Compared to the pristine powder, the monolith exhibited lower specific surface area (about 30% less), total pore volume and pore size (of about 200 Å of width), and bond less SBP under the same experimental conditions. The immobilized SBP products were tested for their catalytic activity in the reaction of hydrogen peroxide, 3-(dimethylamino)benzoic acid (DMAB) and 3-methyl-2-benzothiazolinone hydrazone (MBTH), by comparison with the same reaction performed with native SBP in solution. The reaction performed in the presence of immobilized SBP was slower than that catalyzed by native SBP in solution. However, in spite of its lower SBP content, monolith immobilized SBP (M-SBP) was found kinetically more active than the powder immobilized SBP (P-SBP). Also, M-SBP allowed to achieve the same reagents conversion as native SBP (95% of reagent conversion), although in longer time, whereas the maximum reagent conversion achieved with P-SBP was much lower (75% of reagent conversion). The M-SBP was more easily recovered from the reaction medium and found more stable than P-SBP upon repeated catalyst recycling (after 20 cycles 75–80% of the initial activity was retained by both immobilized samples, slightly higher in the case of M-SBP). 相似文献
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Luisa Diomede Cristina Soria Margherita Romeo Sofia Giorgetti Loredana Marchese Patrizia Palma Mangione Riccardo Porcari Irene Zorzoli Mario Salmona Vittorio Bellotti Monica Stoppini 《PloS one》2012,7(12)
Availability of living organisms to mimic key step of amyloidogenesis of human protein has become an indispensable tool for our translation approach aiming at filling the deep gap existing between the biophysical and biochemical data obtained in vitro and the pathological features observed in patients. Human β2-microglobulin (β2-m) causes systemic amyloidosis in haemodialysed patients. The structure, misfolding propensity, kinetics of fibrillogenesis and cytotoxicity of this protein, in vitro, have been studied more extensively than for any other globular protein. However, no suitable animal model for β2-m amyloidosis has been so far reported. We have now established and characterized three new transgenic C. elegans strains expressing wild type human β2-m and two highly amyloidogenic isoforms: P32G variant and the truncated form ΔN6 lacking of the 6 N-terminal residues. The expression of human β2-m affects the larval growth of C. elegans and the severity of the damage correlates with the intrinsic propensity to self-aggregate that has been reported in previous in vitro studies. We have no evidence of the formation of amyloid deposits in the body-wall muscles of worms. However, we discovered a strict correlation between the pathological phenotype and the presence of oligomeric species recognized by the A11 antibody. The strains expressing human β2-m exhibit a locomotory defect quantified with the body bends assay. Here we show that tetracyclines can correct this abnormality confirming that these compounds are able to protect a living organism from the proteotoxicity of human β2-m. 相似文献
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Microbial diseases occur as a result of multifarious host-pathogen interactions. However, invading pathogens encounter a large number of different harmless and beneficial bacterial species, which colonize and reside in the host. Surprisingly, there has been little study of the possible interactions between incoming pathogens and the resident bacterial community. Recent studies have revealed that resident bacteria assist different types of incoming pathogens via a wide variety of mechanisms including cell-cell signaling, metabolic interactions, evasion of the immune response and a resident-to-pathogen switch. This calls for serious consideration of pathogen-microbe interactions in the host with respect to disease severity and progression. 相似文献