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Izabela Fokt Slawomir Szymanski Stanislaw Skora Marcin Cybulski Timothy Madden Waldemar Priebe 《Carbohydrate research》2009,344(12):340
Modified d-glucose and d-mannose analogs are potentially clinically useful metabolic inhibitors. Biological evaluation of 2-deoxy-2-halo analogs has been impaired by limited availability and lack of efficient methods for their preparation. We have developed practical synthetic approaches to 2-deoxy-2-fluoro-, 2-chloro-2-deoxy-, 2-bromo-2-deoxy-, and 2-deoxy-2-iodo derivatives of d-glucose and d-mannose that exploit electrophilic addition reactions to a commercially available 3,4,6-tri-O-acetyl-d-glucal. 相似文献
84.
Homodimeric receptors with one or two transmembrane (TM) segments per monomer are universal to life and represent the largest and most diverse group of cellular TM receptors. They frequently share domain types across phyla and, in some cases, have been recombined experimentally into functional chimeras (e.g., the bacterial aspartate chemoreceptor with the human insulin receptor), suggesting that they have a common mechanism. The nature of this mechanism, however, is still being debated. We have proposed a new model for transduction mechanism by axial helix rotation, based on the structure of a widespread domain, HAMP, that frequently occurs in direct continuation of the last TM segment, primarily in histidine kinases and chemoreceptors. Here we show by statistical analysis that HAMP domain sequences have biophysical properties compatible with the two conformations proposed by the model. The analysis also identifies three networks of coevolving residues, which allow the mechanism to subdivide into individual steps. The most extended of these networks is specific for membrane-bound HAMP domains and most likely accepts the signal from the TM helices. In a classification based on sequence clustering, these HAMPs form a central supercluster, surrounded by smaller clusters of divergent HAMPs, which typically combine into arrays of up to 31 consecutive copies and accept conformational input from other HAMP domains. Unexpectedly, the classification shows a division between domains of histidine kinases and those of chemoreceptors; thus, except for a few versatile lineages, HAMP domains are largely specific for one particular output domain. Within proteins using a given output domain, HAMP domains also show extensive coevolution with histidine kinases, but not with chemoreceptors. We attribute the greater capability for recombination among chemoreceptors to their acquisition of a reversible modification system, which acts as a capacitor for the initially deleterious effects of combining domains optimized in different contexts. 相似文献
85.
Dornbush PJ Vazquez-Anaya G Shokar A Benson S Rapp M Wnuk SF Wrischnik LA Land KM 《Bioorganic & medicinal chemistry letters》2010,20(24):7466-7468
Trypanosoma brucei and Trichomonas vaginalis are both parasitic protozoans that are known to share many similar biochemical pathways. Aristeromycin, as well as 5'-iodovinyl and 5'-oxime analogues of adenosine, are potent inhibitors of AdoHcy hydrolase in T. brucei, an enzyme that catalyses the hydrolysis of AdoHcy to adenosine and L-homocysteine. To help determine the role of this enzyme in T. vaginalis, we have tested a library of 5'-modified adenosine derivatives, including 5'-deoxy-5'-(iodomethylene)-adenosine and related 6-N-cyclopropyl analogues. Our results indicate that these inhibitors are effective at inhibiting the growth of T. vaginalis, by as much as 95%. 相似文献
86.
Erin E. Connor Stanislaw Kahl Theodore H. Elsasser Joel S. Parker Robert W. Li Curtis P. Van Tassell Ransom L. BaldwinVI Scott M. Barao 《Functional & integrative genomics》2010,10(1):39-51
Growing ruminants under extended dietary restriction exhibit compensatory growth upon ad libitum feeding, which is associated
with increased feed efficiency, lower basal energy requirements, and changes in circulating concentrations of metabolic hormones.
To identify mechanisms contributing to these physiological changes, 8-month-old steers were fed either ad libitum (control;
n = 6) or 60–70% of intake of control animals (feed-restricted; n = 6) for a period of 12 weeks. All steers were fed ad libitum for the remaining 8 weeks of experimentation (realimentation).
Liver was biopsied at days −14, +1, and +14 relative to realimentation for gene expression analysis by microarray hybridization.
During early realimentation, feed-restricted steers exhibited greater rates of gain and feed efficiency than controls and
an increase in expression of genes functioning in cellular metabolism, cholesterol biosynthesis, oxidative phosphorylation,
glycolysis, and gluconeogenesis. Gene expression changes during feed restriction were similar to those reported in mice, indicating
similar effects of caloric restriction across species. Based on expression of genes involved in cell division and growth and
upregulation of genes encoding mitochondrial complex proteins in early realimentation, it was concluded that reduced hepatic
size and increased mitochondrial function may contribute to improved feed efficiency observed during compensatory growth. 相似文献
87.
Stanislaw Schastak Svitlana Ziganshyna Burkhard Gitter Peter Wiedemann Thomas Claudepierre 《PloS one》2010,5(7)
The worldwide rise in the rates of antibiotic resistance of bacteria underlines the need for alternative antibacterial agents. A promising approach to kill antibiotic-resistant bacteria uses light in combination with a photosensitizer to induce a phototoxic reaction. Concentrations of 1, 10 and 100µM of tetrahydroporphyrin-tetratosylat (THPTS) and different incubation times (30, 90 and 180min) were used to measure photodynamic efficiency against two Gram-positive strains of S.aureus (MSSA and MRSA), and two Gram-negative strains of E.coli and P.aeruginosa. We found that phototoxicity of the drug is independent of the antibiotic resistance pattern when incubated in PBS for the investigated strains. Also, an incubation with 100µM THPTS followed by illumination, yielded a 6lg (≥99.999%) decrease in the viable numbers of all bacteria strains tested, indicating that the THPTS drug has a high degree of photodynamic inactivation. We then modulated incubation time, photosensitizer concentration and monitored the effect of serum on the THPTS activity. In doing so, we established the conditions to obtain the strongest bactericidal effect. Our results suggest that this new and highly pure synthetic compound should improve the efficiency of photodynamic therapy against multiresistant bacteria and has a significant potential for clinical applications in the treatment of nosocomial infections. 相似文献
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89.
2-(p-Iodophenyl)-3-(p-nitrophenyl)-5-phenyltetrazolium chloride (INT) dehydrogenase test and RNA assay were introduced to evaluate biomass in the processes of aerobic biodegradation of the organic fraction of municipal solid waste (MSW) in bioreactors. It was found that RNA quantification by KOH/UV method delivered reliable and repeatable results. Relative standard deviation (RSD) for INT test was significantly higher than for RNA assay and achieved values of 3-15%. Moreover, it occurred that the optimum temperature for the growth of autochthonic biomass, which takes part in the biodegradation process, was in the range from 25 to 37 degrees C. 相似文献
90.
Khalili M Saunders JA Liwo A Ołdziej S Scheraga HA 《Protein science : a publication of the Protein Society》2004,13(10):2725-2735
United-residue potentials are derived for interactions of the calcium cation with polypeptide chains in energy-based prediction of protein structure with a united-residue (UNRES) force-field. Specific potentials were derived for the interaction of the calcium cation with the Asp, Glu, Asn, and Gln side chains and the peptide group. The analytical expressions for the interaction energies for each of these amino acids were obtained by averaging the electrostatic interaction energy, expressed by a multipole series over the dihedral angles not considered in the united-residue model, that is, the side-chain dihedral angles chi and the dihedral angles lambda for the rotation of peptide groups about the C(alpha)...C(alpha) virtual-bond axes. For the side-chains that do not interact favorably with calcium, simple excluded-volume potentials were introduced. The parameters of the potentials were obtained from ab initio quantum mechanical calculations of model systems at the Restricted Hartree-Fock (RHF) level with the 6-31G(d,p) basis set. The energy surfaces of pairs consisting of Ca(2+)-acetate, Ca(2+)-propionate, Ca(2+)-acetamide, Ca(2+)-propionamide, and Ca(2+)-N-methylacetamide systems (modeling the Ca(2+)-Asp(-), Ca(2+)-Glu(-), Ca(2+)-Asn, Ca(2+)-Gln, and Ca(2+)-peptide group interactions) at different distances and orientations were calculated. For each pair, the restricted free energy (RFE) surfaces were calculated by numerical integration over the degrees of freedom lost when switching from the all-atom model to the united-residue model. Finally, the analytical expressions for each pair were fitted to the RFE surfaces. This force-field was able to distinguish the EF-hand motif from all potential binding sites in the crystal structures of bovine alpha-lactalbumin, whiting parvalbumin, calbindin D9K, and apo-calbindin D9K. 相似文献