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71.
Beaulieu C Wang Z Denis D Greig G Lamontagne S O'Neill G Slipetz D Wang J 《Bioorganic & medicinal chemistry letters》2004,14(12):3195-3199
A series of 2-substituted N-benzyl benzimidazole containing molecules has been synthesized and its structure-activity relationship for the human DP receptor has been evaluated. Selective DP antagonists with nanomolar potency for the DP receptor were identified in this novel series of benzimidazoles. 相似文献
72.
With the advent of combinatorial chemistry and high throughput screening, a major bottleneck in the pharmaceutical industry has changed from quickly finding active compounds to limiting them to a manageable number for proper follow-up. With hundreds to thousands of active compounds identified by a multitude of biological screens, there need to be rapid and unambiguous methods for eliminating false positive, toxic, or otherwise difficult compounds from further scrutiny. We have used electrospray ionization mass spectrometry as a rapid screening method to identify compounds from viral screens that yield a positive assay response by interaction with DNA rather than inhibiting the target enzyme. Both the sample preparation and data acquisition have been automated, allowing the screening of all hits from relevant biological screens (up to 1,000/week). The assay was validated using several known DNA intercalators and minor groove binders. These "standards" and many but not all of our "active compounds" were shown to form noncovalent complexes with a variety of different DNA:DNA and DNA:RNA duplexes. 相似文献
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Judge J Kyriazakis I Greig A Allcroft DJ Hutchings MR 《Applied and environmental microbiology》2005,71(10):6033-6038
Clustering of pathogens in the environment leads to hot spots of diseases at local, regional, national, and international levels. Scotland contains regional hot spots of Johne's disease (caused by Mycobacterium avium subsp. paratuberculosis) in rabbits, and there is increasing evidence of a link between paratuberculosis infections in rabbits and cattle. The spatial and temporal dynamics of paratuberculosis in rabbits within a hot spot region were studied with the overall aim of determining environmental patterns of infection and thus the risk of interspecies transmission to livestock. The specific aims were to determine if prevalence of paratuberculosis in rabbits varies temporally between seasons and whether the heterogeneous spatial environmental distribution of M. avium subsp. paratuberculosis on a large scale (i.e., regional hot spots) is replicated at finer resolutions within a hot spot. The overall prevalence of M. avium subsp. paratuberculosis in rabbits was 39.7%; the temporal distribution of infection in rabbits followed a cyclical pattern, with a peak in spring of 55.4% and a low in summer of 19.4%. Spatially, M. avium subsp. paratuberculosis-infected rabbits and, thus, the risk of interspecies transmission were highly clustered in the environment. However, this is mostly due to the clustered distribution of rabbits. The patterns of M. avium subsp. paratuberculosis infection in rabbits are discussed in relation to the host's socioecology and risk to livestock. 相似文献
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A 20-month-old child was accidentally poisoned after biting through the bottom of a medicine container and ingesting the tablets inside. Consequently a study was carried out to determine the force required to fracture 20 randomly selected 25 and 32 ml polystyrene containers to see whether this exceeded the bite force of a child''s jaw. Tests were performed at displacement rates of 0.5 and 10 cm/min. All the containers failed at well below the bite force recorded for children, which is 392 N. All containers must conform to a British Standards test that requires that they withstand a force of only 35 N. Clearly this is not enough to safeguard small children. The use of polystyrene containers should be scrutinised closely, as the case of accidental poisoning reported may not be unique. 相似文献
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Tariq M. Butt Bethany P. J. Greenfield Carolyn Greig Thierry G. G. Maffeis James W. D. Taylor Justyna Piasecka Ed Dudley Ahmed Abdulla Ivan M. Dubovskiy Inmaculada Garrido-Jurado Enrique Quesada-Moraga Mark W. Penny Daniel C. Eastwood 《PloS one》2013,8(12)
Metarhizium anisopliae, a fungal pathogen of terrestrial arthropods, kills the aquatic larvae of Aedes aegypti, the vector of dengue and yellow fever. The fungus kills without adhering to the host cuticle. Ingested conidia also fail to germinate and are expelled in fecal pellets. This study investigates the mechanism by which this fungus adapted to terrestrial hosts kills aquatic mosquito larvae. Genes associated with the M. anisopliae early pathogenic response (proteinases Pr1 and Pr2, and adhesins, Mad1 and Mad2) are upregulated in the presence of larvae, but the established infection process observed in terrestrial hosts does not progress and insecticidal destruxins were not detected. Protease inhibitors reduce larval mortality indicating the importance of proteases in the host interaction. The Ae. aegypti immune response to M. anisopliae appears limited, whilst the oxidative stress response gene encoding for thiol peroxidase is upregulated. Cecropin and Hsp70 genes are downregulated as larval death occurs, and insect mortality appears to be linked to autolysis through caspase activity regulated by Hsp70 and inhibited, in infected larvae, by protease inhibitors. Evidence is presented that a traditional host-pathogen response does not occur as the species have not evolved to interact. M. anisopliae retains pre-formed pathogenic determinants which mediate host mortality, but unlike true aquatic fungal pathogens, does not recognise and colonise the larval host. 相似文献
80.
Alixe H. M. Kilgour Iain J. Gallagher Alasdair M. J. MacLullich Ruth Andrew Calum D. Gray Philippa Hyde Henning Wackerhage Holger Husi James A. Ross John M. Starr Karen E. Chapman Kenneth C. H. Fearon Brian R. Walker Carolyn A. Greig 《PloS one》2013,8(12)