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111.
James B. Gerken Colin W. Anson Yuliya Preger Peter G. Symons J. David Genders Yang Qiu Wenzhen Li Thatcher W. Root Shannon S. Stahl 《Liver Transplantation》2020,10(20)
Quinones are appealing targets as organic charge carriers for aqueous redox flow batteries (RFBs), but their utility continues to be constrained by limited stability under operating conditions. The present study evaluates the stability of a series of water‐soluble quinones, with redox potentials ranging from 605–885 mV versus NHE, under acidic aqueous conditions (1 m H2SO4). Four of the quinones are examined as cathodic electrolytes in an aqueous RFB, paired with anthraquinone‐2,7‐disulfonate as the anodic electrolyte. The RFB data complement other solution stability tests and show that the most stable electrolyte is a tetrasubstituted quinone containing four sulfonated thioether substituents. The results highlight the importance of substituting all C–H positions of the quinone in order to maximize the quinone stability and set the stage for design of improved organic electrolytes for aqueous RFBs. 相似文献
112.
Andrews MD Fish PV Blagg J Brabham TK Brennan PE Bridgeland A Brown AD Bungay PJ Conlon KM Edmunds NJ af Forselles K Gibbons CP Green MP Hanton G Holbrook M Jessiman AS McIntosh K McMurray G Nichols CL Root JA Storer RI Sutton MR Ward RV Westbrook D Whitlock GA 《Bioorganic & medicinal chemistry letters》2011,21(9):2715-2720
New pyrimido[4,5-d]azepines 7 are disclosed as potent 5-HT2C receptor agonists. A preferred example, 7b had minimal activation at either the 5-HT2A or 5-HT2B receptors combined with robust efficacy in a preclinical canine model of stress urinary incontinence (SUI) and attractive pharmacokinetic and safety properties. Based on this profile, 7b (PF-3246799) was identified as a candidate for clinical development for the treatment of SUI. In addition, it proved to be critical to build an understanding of the translation between recombinant cell-based systems, native tissue preparations and in vivo preclinical models. This was a significant undertaking and proved to be crucial in compound selection. 相似文献
113.
Newton RJ Vandewalle JL Borchardt MA Gorelick MH McLellan SL 《Applied and environmental microbiology》2011,77(19):6972-6981
The complexity of fecal microbial communities and overlap among human and other animal sources have made it difficult to identify source-specific fecal indicator bacteria. However, the advent of next-generation sequencing technologies now provides increased sequencing power to resolve microbial community composition within and among environments. These data can be mined for information on source-specific phylotypes and/or assemblages of phylotypes (i.e., microbial signatures). We report the development of a new genetic marker for human fecal contamination identified through microbial pyrotag sequence analysis of the V6 region of the 16S rRNA gene. Sequence analysis of 37 sewage samples and comparison with database sequences revealed a human-associated phylotype within the Lachnospiraceae family, which was closely related to the genus Blautia. This phylotype, termed Lachno2, was on average the second most abundant fecal bacterial phylotype in sewage influent samples from Milwaukee, WI. We developed a quantitative PCR (qPCR) assay for Lachno2 and used it along with the qPCR-based assays for human Bacteroidales (based on the HF183 genetic marker), total Bacteroidales spp., and enterococci and the conventional Escherichia coli and enterococci plate count assays to examine the prevalence of fecal and human fecal pollution in Milwaukee's harbor. Both the conventional fecal indicators and the human-associated indicators revealed chronic fecal pollution in the harbor, with significant increases following heavy rain events and combined sewer overflows. The two human-associated genetic marker abundances were tightly correlated in the harbor, a strong indication they target the same source (i.e., human sewage). Human adenoviruses were routinely detected under all conditions in the harbor, and the probability of their occurrence increased by 154% for every 10-fold increase in the human indicator concentration. Both Lachno2 and human Bacteroidales increased specificity to detect sewage compared to general indicators, and the relationship to a human pathogen group suggests that the use of these alternative indicators will improve assessments for human health risks in urban waters. 相似文献
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Human immunodeficiency virus type 1 cDNAs produced in the presence of APOBEC3G exhibit defects in plus-strand DNA transfer and integration 总被引:12,自引:10,他引:2
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Mbisa JL Barr R Thomas JA Vandegraaff N Dorweiler IJ Svarovskaia ES Brown WL Mansky LM Gorelick RJ Harris RS Engelman A Pathak VK 《Journal of virology》2007,81(13):7099-7110
Encapsidation of host restriction factor APOBEC3G (A3G) into vif-deficient human immunodeficiency virus type 1 (HIV-1) blocks virus replication at least partly by C-to-U deamination of viral minus-strand DNA, resulting in G-to-A hypermutation. A3G may also inhibit HIV-1 replication by reducing viral DNA synthesis and inducing viral DNA degradation. To gain further insight into the mechanisms of viral inhibition, we examined the metabolism of A3G-exposed viral DNA. We observed that an overall 35-fold decrease in viral infectivity was accompanied by a five- to sevenfold reduction in viral DNA synthesis. Wild-type A3G induced an additional fivefold decrease in the amount of viral DNA that was integrated into the host cell genome and similarly reduced the efficiency with which HIV-1 preintegration complexes (PICs) integrated into a target DNA in vitro. The A3G C-terminal catalytic domain was required for both of these antiviral activities. Southern blotting analysis of PICs showed that A3G reduced the efficiency and specificity of primer tRNA processing and removal, resulting in viral DNA ends that are inefficient substrates for integration and plus-strand DNA transfer. However, the decrease in plus-strand DNA transfer did not account for all of the observed decrease in viral DNA synthesis associated with A3G. These novel observations suggest that HIV-1 cDNA produced in the presence of A3G exhibits defects in primer tRNA processing, plus-strand DNA transfer, and integration. 相似文献
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118.
Arangassery Rosemary Bastian Aakansha Nangarlia Lauren D. Bailey Andrew Holmes R. Venkat Kalyana Sundaram Charles Ang Diogo R. M. Moreira Kevin Freedman Caitlin Duffy Mark Contarino Cameron Abrams Michael Root Irwin Chaiken 《The Journal of biological chemistry》2015,290(1):529-543
Entry of HIV-1 into host cells remains a compelling yet elusive target for developing agents to prevent infection. A peptide triazole (PT) class of entry inhibitor has previously been shown to bind to HIV-1 gp120, suppress interactions of the Env protein at host cell receptor binding sites, inhibit cell infection, and cause envelope spike protein breakdown, including gp120 shedding and, for some variants, virus membrane lysis. We found that gold nanoparticle-conjugated forms of peptide triazoles (AuNP-PT) exhibit substantially more potent antiviral effects against HIV-1 than corresponding peptide triazoles alone. Here, we sought to reveal the mechanism of potency enhancement underlying nanoparticle conjugate function. We found that altering the physical properties of the nanoparticle conjugate, by increasing the AuNP diameter and/or the density of PT conjugated on the AuNP surface, enhanced potency of infection inhibition to impressive picomolar levels. Further, compared with unconjugated PT, AuNP-PT was less susceptible to reduction of antiviral potency when the density of PT-competent Env spikes on the virus was reduced by incorporating a peptide-resistant mutant gp120. We conclude that potency enhancement of virolytic activity and corresponding irreversible HIV-1 inactivation of PTs upon AuNP conjugation derives from multivalent contact between the nanoconjugates and metastable Env spikes on the HIV-1 virus. The findings reveal that multispike engagement can exploit the metastability built into virus the envelope to irreversibly inactivate HIV-1 and provide a conceptual platform to design nanoparticle-based antiviral agents for HIV-1 specifically and putatively for metastable enveloped viruses generally. 相似文献
119.
Macroevolution and climate change influence phylogenetic community assembly of North American hoofed mammals
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Danielle Fraser Root Gorelick Natalia Rybczynski 《Biological journal of the Linnean Society. Linnean Society of London》2015,114(3):485-494
Animal richness, community composition, and phylogenetic community structure (PCS) vary across the modern landscape. Animal communities vary from phylogenetically clustered (i.e. higher relatedness amongst co‐occurring species than is expected by chance) to phylogenetically even (i.e. co‐occurring taxa are more distantly related than expected by chance), which is explained by abiotic or climatic filtering and competitive exclusion, respectively. Under this model, the contribution of historical origination and extinction events to modern animal PCS remains relatively unknown. Because origination and extinction determine the make‐up of the terrestrial community, the study of historical changes in animal PCS is tantamount to understanding formation of modern communities. In the present study, we test the effects of macroevolution and climate changes on ‘hoofed mammals’ (i.e. perissodactyl and artiodactyl) PCS from the late Cenozoic of North America because they experience large, phylogenetically dispersed extinctions of browsing species and phylogenetically dispersed originations of grazing species associated with the evolution of grassland ecosystems during the late Miocene. We show that the loss of numerically dominant nonhypsodont (putatively browsing and mixed feeding) clades and phylogenetically dispersed origination of less speciose clades following the mid Miocene climatic optimum led to an increase in phylogenetic evenness at the regional scale that is well explained by global climate changes. Phylogenetic evenness and a reduced richness during the late Cenozoic may have facilitated reduced niche overlap among co‐occurring hoofed mammal species as global climates cooled. © 2015 The Linnean Society of London, Biological Journal of the Linnean Society, 2015, 114 , 485–494. 相似文献
120.
J. Jeffrey Root Kevin T. Bentler Susan A. Shriner Nicole L. Mooers Kaci K. VanDalen Heather J. Sullivan Alan B. Franklin 《PloS one》2014,9(8)