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971.
The importance of conserved inner saccharide epitopes to the immune performance of meningococcal lipooligosaccharide-protein conjugate vaccines was demonstrated in the following experiments. Two different oligosaccharides were obtained by chemical degradations of the same L7 lipooligosaccharide, and both were linked terminally to tetanus toxoid. One was a truncated oligosaccharide in which the inner epitopes were incomplete and was obtained by mild acid hydrolysis of the L7 lipooligosaccharide. This oligosaccharide was conjugated by direct reductive amination through its newly exposed terminal Kdo residue. The second, a full-length oligosaccharide, was obtained by O-deacylation of the L7 lipooligosaccharide, with subsequent removal of phosphate substituents from its lipid A moiety using alkaline phosphatase. This permitted the full-length oligosaccharide to be conjugated directly to tetanus toxoid by reductive amination through its newly exposed terminal 2-N-acyl-2-deoxy-D-glucopyranose residue. Comparison of the immune performance of the two conjugates in mice revealed, that while both were able to induce significant levels of L7-lipooligosaccharide-specific IgG antibody, the conjugate made with the full-length saccharide was able to induce antibodies with increased bactericidal activity against homologous meningococci. 相似文献
972.
973.
Macrolide antibiotics like erythromycin can induce the synthesis of a specific 23S rRNA methyltransferase which confers resistance to cells containing the erm gene. Erythromycin inhibits both protein synthesis and the formation of 50S subunits in bacterial cells. We have tested the idea that the 50S precursor particle that accumulates in antibiotic-treated Staphylococcus aureus cells is a substrate for the methyltransferase enzyme. Pulse-chase labeling studies were conducted to examine the rates of ribosomal subunit formation in control and erythromycin-induced cells. Erythromycin binding to 50S subunits was examined under the same conditions. The rate of 50S subunit formation was reduced for up to 30 min after antibiotic addition, and erythromycin binding was substantial at this time. A nuclease protection assay was used to examine the methylation of adenine 2085 in 23S rRNA after induction. A methyl-labeled protected RNA sequence was found to appear in cells 30 min after induction. This protected sequence was found in both 50S subunits and in a subunit precursor particle sedimenting at about 30S in sucrose gradients. 23S rRNA isolated from 50S subunits of cells could be labeled by a ribosome-associated methlytransferase activity, with (3)H-S-adenosylmethionine as a substrate. 50S subunits were not a substrate for the enzyme, but the 30S gradient region from erythromycin-treated cells contained a substrate for this activity. These findings are consistent with a model that suggests that antibiotic inhibition of 50S formation leads to the accumulation of a precursor whose 23S rRNA becomes methylated by the induced enzyme. The methylated rRNA will preclude erythromycin binding; thus, assembly of the particle and translation become insensitive to the inhibitory effects of the drug. 相似文献
974.
Nitrite served as an energy-conserving electron acceptor for the acetogenic bacterium Moorella thermoacetica. Growth occurred in an undefined (0.1% yeast extract) medium containing 20 m M glyoxylate and 5 m M nitrite and was essentially equivalent to that observed in the absence of nitrite. In the presence of nitrite, acetate (the normal product of glyoxylate-derived acetogenesis) was not detected during growth. Instead, growth was coupled to nitrite dissimilation to ammonium, and acetogenesis was limited to the stationary phase. Furthermore, membranes from glyoxylate-grown cells under nitrite-dissimilating conditions were deficient in the b-type cytochrome that is typically found in the membranes of acetogenic cells. Unlike glyoxylate, other acetogenic substrates (fructose, oxalate, glycolate, vanillin, and hydrogen) were not growth supportive in the undefined medium containing nitrite, and glyoxylate-dependent growth did not occur in a nitrite-supplemented, basal (without yeast extract) medium. Glyoxylate-dependent growth by Moorella thermoautotrophica was not observed in the undefined medium containing nitrite. 相似文献
975.
976.
U.S. Human immunodeficiency virus type 1 epidemic: date of origin,population history,and characterization of early strains
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Robbins KE Lemey P Pybus OG Jaffe HW Youngpairoj AS Brown TM Salemi M Vandamme AM Kalish ML 《Journal of virology》2003,77(11):6359-6366
Human immunodeficiency virus (HIV) type 1 subtype B sequences (whole envelope and the p17 region of gag) were obtained from peripheral blood mononuclear cell samples collected in 1981 from seven HIV-infected U.S. individuals and in 1982 from one infected Canadian resident. Phylogenetic and nucleotide distance analyses were performed by using database sequences representing North American strains collected from 1978 to 1995. The estimated phylogeny was starlike, with early strains represented on different lineages. When sequences were grouped by years of collection, nucleotide distance comparisons demonstrated an increase in diversity over time and indicated that contemporary strains are more closely related to early epidemic strains than to each other. Using a recently developed likelihood ratio reduction procedure, the date of origin of the U.S. epidemic was estimated to be 1968 +/- 1.4 years. A coalescent approach was also used to estimate the population history of the U.S. subtype B epidemic. Our analyses provide new information that implies an exponential growth rate from the beginning of the U.S. HIV epidemic. The dating results suggest a U.S. introduction date (or date of divergence from the most recent common ancestor) that precedes the date of the earliest known AIDS cases in the late 1970s. Furthermore, the estimated epidemic growth curve shows a period of exponential growth that preceded most of the early documented cases and also indicates a leveling of prevalence rates in the recent past. 相似文献
977.
A nonlinear optimization technique, in conjunction with a single-nephron, single-solute mathematical model of the quail urine
concentrating mechanism, was used to estimate parameter sets that optimize a measure of concentrating mechanism efficiency,
viz., the ratio of the free-water absorption rate to the total NaCl active transport rate. The optimization algorithm, which is
independent of the numerical method used to solve the model equations, runs in a few minutes on a 1000 MHz desktop computer.
The parameters varied were: tubular permeabilities to water and solute; maximum active solute transport rates of the ascending
limb of Henle and the collecting duct (CD); length of the prebend enlargement (PBE) of the descending limb; fractional solute
delivery to the CD; solute concentration of tubular fluid entering the CD at the cortico-medullary boundary; and rate of exponential
CD population decrease along the medullary cone. Using a base-case parameter set and parameter bounds suggested by physiologic
experiments, the optimization algorithm identified a maximum-efficiency set of parameter values that increased efficiency
by 40% above base-case efficiency; a minimum-efficiency set reduced efficiency by about 41%. When maximum-efficiency parameter
values were computed as medullary length varied over the physiologic range, the PBE was found to make up 88% of a short medullary
cone but only 8% of a long medullary cone. 相似文献
978.
Recombinant mammalian proteins expressed in E. coli can be difficult to purify in high yield in a soluble and functional form. Various techniques have been described to prevent proteolysis of expressed proteins and/or their sequestering as insoluble aggregates within inclusion bodies. We report conditions for expressing recombinant proteins from E. coli that significantly enhanced the yield of soluble and functional protein. We demonstrate high-yield recovery of a native, high-molecular-weight RNA binding protein without the aid of fusion protein sequence. The principle factor that increased protein yield was the induction of protein expression in a late log phase culture, although reduced temperature during the induction and a low IPTG concentration also contributed to a higher yield. 相似文献
979.
Sanchez-Martinez C Shih C Faul MM Zhu G Paal M Somoza C Li T Kumrich CA Winneroski LL Xun Z Brooks HB Patel BK Schultz RM DeHahn TB Spencer CD Watkins SA Considine E Dempsey JA Ogg CA Campbell RM Anderson BA Wagner J 《Bioorganic & medicinal chemistry letters》2003,13(21):3835-3839
The synthesis of new analogues of Arcyriaflavin A in which one indole ring is replaced by an aryl or heteroaryl ring is described. These new series of aryl[a]pyrrolo[3,4-c]carbazoles were evaluated as inhibitors of Cyclin D1-CDK4. A potent and selective D1-CDK4 inhibitor, 7a (D1-CDK4 IC(50)=45 nM), has been identified. The potency, selectivity profile against other kinases, and structure-activity relationship (SAR) trends of this class of compounds are discussed. 相似文献
980.
Zhu G Conner S Zhou X Shih C Brooks HB Considine E Dempsey JA Ogg C Patel B Schultz RM Spencer CD Teicher B Watkins SA 《Bioorganic & medicinal chemistry letters》2003,13(7):1231-1235
A novel series of pyrrolo[3,4-c] carbazoles fused with a quinolinyl/isoquinolinyl moiety were synthesized and their D1/CDK4 inhibitory and antiproliferative activity were evaluated. Compound 8H, 14H-isoquinolinyl[6,5-a]-pyrrolo[3,4-c]carbazole-7,9-dione (1d) was found to be a highly potent D1/CDK4 inhibitor with an IC(50) of 69 nM. Compound 1d also inhibited tumor cell growth, arrested tumor cells in G1 phase and inhibited pRb phosphorylation. 相似文献