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911.
912.
Emily A. Sloan Mary F. Kearney Laurie R. Gray Kathryn Anastos Eric S. Daar Joseph Margolick Frank Maldarelli Marie-Louise Hammarskjold David Rekosh 《Journal of virology》2013,87(20):11173-11186
HIV-1 Rev and the Rev response element (RRE) enable a critical step in the viral replication cycle by facilitating the nuclear export of intron-containing mRNAs, yet their activities have rarely been analyzed in natural infections. This study characterized their genetic and functional variation in a small cohort of HIV-infected individuals. Multiple Rev and RRE sequences were obtained using single-genome sequencing (SGS) of plasma samples collected within 6 months after seroconversion and at a later time. This allowed the identification of cognate sequences that were linked in vivo in the same viral genome and acted together as a functional unit. Phylogenetic analyses of these sequences indicated that 4/5 infections were founded by a single transmission event. Rev and RRE variants from each time point were subjected to functional analysis as both cognate pairs and as individual components. While a range of Rev-RRE activities were seen, the activity of cognate pairs from a single time point clustered to a discrete level, which was termed the set point. In 3/5 patients, this set point changed significantly over the time period studied. In all patients, RRE activity was more sensitive to sequence variation than Rev activity and acted as the primary driver of the cognate set point. Selected patient RREs were also shown to have differences in Rev multimerization using gel shift binding assays. Thus, rather than acting as a simple on-off switch or maintaining a constant level of activity throughout infection, the Rev-RRE system can fluctuate, presumably to control replication. 相似文献
913.
914.
Katherine E. Price Giulia Orazi Kathryn L. Ruoff Wesley P. Hebert George A. O’Toole Paul Mastoridis 《PloS one》2015,10(10)
Cystic Fibrosis (CF) is a human genetic disease that results in the accumulation of thick, sticky mucus in the airways, which results in chronic, life-long bacterial biofilm infections that are difficult to clear with antibiotics. Pseudomonas aeruginosa lung infection is correlated with worsening lung disease and P. aeruginosa transitions to an antibiotic tolerant state during chronic infections. Tobramycin is an aminoglycoside currently used to combat lung infections in individuals with CF. While tobramycin is effective at eradicating P. aeruginosa in the airways of young patients, it is unable to completely clear the chronic P. aeruginosa infections in older patients. A recent report showed that co-addition of tobramycin and mannitol enhanced killing of P. aeruginosa grown in vitro as a biofilm on an abiotic surface. Here we employed a model system of bacterial biofilms formed on the surface of CF-derived airway cells to determine if mannitol would enhance the antibacterial activity of tobramycin against P. aeruginosa grown on a more clinically relevant surface. Using this model system, which allows the growth of robust biofilms with high-level antibiotic tolerance analogous to in vivo biofilms, we were unable to find evidence for enhanced antibacterial activity of tobramycin with the addition of mannitol, supporting the observation that this type of co-treatment failed to reduce the P. aeruginosa bacterial load in a clinical setting. 相似文献
915.
Monomeric Ca2+-ATPase of skeletal muscle sarcoplasmic reticulum dispersed in Triton X-100 is stoichiometrically phosphorylated from Pi in a Ca2+-depleted medium containing dimethyl sulfoxide and catalyzes efficient (80%) phosphoryl transfer to ADP following a jump in water activity in the presence of Ca2+. The Ca2+ concentration dependence of ATP synthesis was sigmoidal (nH = 1.7) and in the millimolar range (K0.5 = 0.3 mM), indicating the involvement of at least two low affinity Ca2+ binding sites. These results, taken together with the properties of the monomer in the forward direction of catalysis, show that the catalytic cycle of the detergent-solubilized monomer is essentially the same as that of the membrane enzyme. The substrate and ion specificity of the catalytic intermediates suggest that the monomer is capable of coupled vectorial transport of Ca2+. 相似文献
916.
D B McIntosh 《The Journal of biological chemistry》1992,267(31):22328-22335
It has been shown previously that glutaraldehyde cross-links the Ca(2+)-ATPase of sarcoplasmic reticulum intramolecularly at the active site, involving residues participating in nucleotide binding and the conformational change that results in Ca2+ release to the vesicle lumen and formation of ADP-insensitive E2-P (Ross, D. C., Davidson, G. A., and McIntosh, D. B. (1991) J. Biol. Chem. 266, 4613-4621). This study shows that 10 nmol of [14C]glutaraldehyde/mg of protein attached irreversibly to the ATPase under conditions optimal for formation of the intramolecular cross-link. Half of this amount (i.e. 1 mol/mol ATPase) was inhibited by nucleotide binding. Thermolysin digestion of derivatized vesicles released two nucleotide-sensitive 14C-labeled species, which were isolated and identified as FSRDR*S AND FSRDR*S FA* FA*VEPS where the missing residues are Lys-492 and Arg-678. The majority of the 14C label was released in the sixth cycle of both Edman degradations, confirming the cross-link position. Lys-492 and Arg-678 are evidently close together in the active site, but their distance apart in the linear sequence suggests that they may arise from separate domains, which together constitute an ATP binding cleft. Residues in both regions, and Lys-492 in particular (McIntosh, D.B., Woolley, D.G., and Berman, M.C. (1992) J. Biol. Chem. 267, 5301-5309), have been derivatized by nucleotide-based affinity probes. Mutations of both of these residues in some of the bacterial P-type ATPases suggest that they do not play an essential catalytic role, and the inability of the cross-linked ATPase to form E2-P and to release Ca2+ to the lumen is probably because an essential tertiary structural movement at the active site is blocked. 相似文献
917.
918.
Enzymes for microtubule-dependent motility 总被引:16,自引:0,他引:16
919.
920.
When is a native species invasive? Incursion of a novel predatory marsupial detected using molecular and historical data 下载免费PDF全文
Catriona D. Campbell Stephen D. Sarre Dejan Stojanovic Bernd Gruber Kathryn Medlock Stephen Harris Anna J. MacDonald Clare E. Holleley 《Diversity & distributions》2018,24(6):831-840