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Efficient and error-free replication past a minor-groove DNA adduct by the sequential action of human DNA polymerases iota and kappa 下载免费PDF全文
Washington MT Minko IG Johnson RE Wolfle WT Harris TM Lloyd RS Prakash S Prakash L 《Molecular and cellular biology》2004,24(13):5687-5693
DNA polymerase iota (Poliota) is a member of the Y family of DNA polymerases, which promote replication through DNA lesions. The role of Poliota in lesion bypass, however, has remained unclear. Poliota is highly unusual in that it incorporates nucleotides opposite different template bases with very different efficiencies and fidelities. Since interactions of DNA polymerases with the DNA minor groove provide for the nearly equivalent efficiencies and fidelities of nucleotide incorporation opposite each of the four template bases, we considered the possibility that Poliota differs from other DNA polymerases in not being as sensitive to distortions of the minor groove at the site of the incipient base pair and that this enables it to incorporate nucleotides opposite highly distorting minor-groove DNA adducts. To check the validity of this idea, we examined whether Poliota could incorporate nucleotides opposite the gamma-HOPdG adduct, which is formed from an initial reaction of acrolein with the N(2) of guanine. We show here that Poliota incorporates a C opposite this adduct with nearly the same efficiency as it does opposite a nonadducted template G residue. The subsequent extension step, however, is performed by Polkappa, which efficiently extends from the C incorporated opposite the adduct. Based upon these observations, we suggest that an important biological role of Poliota and Polkappa is to act sequentially to carry out the efficient and accurate bypass of highly distorting minor-groove DNA adducts of the purine bases. 相似文献
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Dedova IV Nikolaeva OP Mikhailova VV dos Remedios CG Levitsky DI 《Biophysical chemistry》2004,110(1-2):119-128
Differential scanning calorimetry was used to examine the effects of cofilin on the thermal unfolding of actin. Stoichiometric binding increases the thermal stability of both G- and F-actin but at sub-saturating concentrations cofilin destabilizes F-actin. At actin:cofilin molar ratios of 1.5-6 the peaks corresponding to stabilized (66-67 degrees C) and destabilized (56-57 degrees C) F-actin are observed simultaneously in the same thermogram. Destabilizing effects of sub-saturating cofilin are highly cooperative and are observed at actin:cofilin molar ratios as low as 100:1. These effects are abolished by the addition of phalloidin or aluminum fluoride. Conversely, at saturating concentrations, cofilin prevents the stabilizing effects of phalloidin and aluminum fluoride on the F-actin thermal unfolding. These results suggest that cofilin stabilizes those actin subunits to which it directly binds, but destabilizes F-actin with a high cooperativity in neighboring cofilin-free regions. 相似文献
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Following incubation of mesophilic methanogenic floccular sludge from a lab-scale upflow anaerobic sludge bed reactor used to treat cattle manure wastewater, a stable 5-aminosalicylate-degrading enrichment culture was obtained. Subsequently, a Citrobacter freundii strain, WA1, was isolated from the 5-aminosalicylate-degrading methanogenic consortium. The methanogenic enrichment culture degraded 5-aminosalicylate completely to CH4, CO2 and NH4
+, while C. freundii strain WA1 reduced 5-aminosalicylate with simultaneous deamination to 2-hydroxybenzyl alcohol during anaerobic growth with electron donors such as pyruvate, glucose or serine. When grown on pyruvate, C. freundii WA1 converted 3-aminobenzoate to benzyl alcohol and also reduced benzaldehyde to benzyl alcohol. Pyruvate was fermented to acetate, CO2, H2 and small amounts of lactate, succinate and formate. Less lactate (30%) was produced from pyruvate when C. freundii WA1 grew with 5-aminosalicylate as co-substrate. 相似文献
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Terenetskaya I 《The Journal of steroid biochemistry and molecular biology》2004,(1-5):623-626
Excessive UV exposures are commonly associated with adverse health effects, but proper amounts of UV are beneficial for people and essential in the natural production of Vitamin D(3) in skin. Two methods have been developed for direct evaluation of the Vitamin D synthetic capacity of sunlight (and artificial UV sources). The first one uses an in vitro model of Vitamin D(3) synthesis (ethanol solution of 7-dehydrocholesterol, 7-DHC), and concentration of previtamin D(3) accumulated during an UV exposure is determined using specially designed spectrophotometric analysis. The second method utilizes photoisomerization of provitamin D in nematic liquid crystalline (LC) matrix, and visual estimation of accumulated previtamin D becomes possible due to special design of a LC cell. This user-friendly method is appropriate for personal UV dosimetry and may have wide application in tanning saloons, in clinical dermatology and UV therapy. 相似文献
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Kristal BS Stavrovskaya IG Narayanan MV Krasnikov BF Brown AM Beal MF Friedlander RM 《Journal of bioenergetics and biomembranes》2004,36(4):309-312
Mitochondria serve as checkpoints and amplifiers on cell death pathways. In the central nervous system, mitochondrial involvement seems essential for normal expression of cell death phenotypes, and interference with these pathways thus seems a reasonable approach to neuroprotection. We have been involved in examining the potential involvement of the mitochondrial permeability transition (mPT) as one of several possible mechanisms by which mitochondria may be drawn into these death cascades. This possibility, though still controversial, is supported by evidence that factors that may stimulate mPT induction are associated with some forms of cell death (e.g., in stroke) and are modulated by diseases of the central nervous system (e.g., Huntington's). Evidence of neuroprotection seen with compounds such as N-Met-Val cyclosporine also support this possibility. 相似文献
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Veinberg G Shestakova I Vorona M Kanepe I Domrachova I Lukevics E 《Bioorganic & medicinal chemistry letters》2004,14(4):1007-1010
Doxorubicin-cephalosporin prodrug adapted to the development of elastases for the liberation of parent drug was synthesized on the basis of cephalosporanate sulfone esters. 相似文献