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161.
The development of effective clinical interventions against multidrug resistance (MDR) in cancer remains a significant challenge.
Single nucleotide polymorphisms (SNPs) contribute to wide variations in how individuals respond to medications and there are
several SNPs in human P-glycoprotein (P-gp) that may influence the interactions of drug-substrates with the transporter. Interestingly,
even some of the synonymous SNPs have functional consequences for P-gp. It is also becoming increasingly evident that an understanding
of the transport pathway of P-gp may be necessary to design effective modulators. In this review we discuss: (1) The potential
importance of SNPs (both synonymous and non-synonymous) in MDR and (2) How new concepts that have emerged from structural
studies with isolated nucleotide binding domains of bacterial ABC transporters have prompted biochemical studies on P-gp,
leading to a better understanding of the mechanism of P-gp mediated transport. Our results suggest that the power-stroke is
provided only after formation of the pre-hydrolysis transition-like (E·S) state during ATP hydrolysis. 相似文献
162.
163.
Succinic acid production from wheat using a biorefining strategy 总被引:2,自引:0,他引:2
The biosynthesis of succinic acid from wheat flour was investigated in a two-stage bio-process. In the first stage, wheat
flour was converted into a generic microbial feedstock either by fungal fermentation alone or by combining fungal fermentation
for enzyme and fungal bio-mass production with subsequent flour hydrolysis and fungal autolysis. In the second stage, the
generic feedstock was converted into succinic acid by bacterial fermentation by Actinobacillus succinogenes. Direct fermentation of the generic feedstock produced by fungal fermentation alone resulted in a lower succinic acid production,
probably due to the low glucose and nitrogen concentrations in the fungal broth filtrate. In the second feedstock production
strategy, flour hydrolysis conducted by mixing fungal broth filtrate with wheat flour generated a glucose-rich stream, while
the fungal bio-mass was subjected to autolysis for the production of a nutrient-rich stream. The possibility of replacing
a commercial semi-defined medium by these two streams was investigated sequentially. A. succinogenes fermentation using only the wheat-derived feedstock resulted in a succinic acid concentration of almost 16 g l–1 with an overall yield of 0.19 g succinic acid per g wheat flour. These results show that a wheat-based bio-refinery employing
coupled fungal fermentation and subsequent flour hydrolysis and fungal autolysis can lead to a bacterial feedstock for the
efficient production of succinic acid. 相似文献
164.
Efficient enzyme catalyzed kinetic resolutions of a synthetically useful chiral building block, (Z)-4-triphenylmethoxy-2,3-epoxybutan-1-ol, are reported. The highest selectivities were achieved by Lipozyme TL IM and Amano Lipase PS enzymes in the presence of vinyl acetate. Enantiomeric enrichment of the optically active acetate isomer was accomplished by selective crystallization of the racemic part of the enantiomeric mixture. Enzyme catalyzed hydrolysis of the acetate also provided an optically pure epoxybutanol derivative. O-Benzylation of (+)-(Z)-1-hydroxy-4-triphenylmethoxy-2,3-epoxybutane followed by super base promoted diastereo- and enantio-selective rearrangement resulted in (+)-(2R,3R,1'R)-3-[1-hydroxy-2-(triphenylmethoxy)ethyl]-2-phenyloxetane in >98% ee and de. Configurations of the new optically active products were determined by chemical correlation. 相似文献
165.
Hui Zou Wen-Quan Liang Qi-Liang Wu Li Zhou Xiao-Hua Hou Na Liu Zong-Quan Wu 《Chirality》2022,34(1):61-69
Helical polymers present some interesting and distinctive properties, and one of the most distinguished applications of them is the chiral recognition and resolution of enantiomers. In this work, star-shaped hybrid helical poly (phenyl isocyanide) (PPI) with polyhedral oligomeric silsesquioxanes (POSS) as the core was designed and synthesized by “grafting to” strategy. The homoarm star-shaped hybrid POSS-(PPI)8 was first obtained by the click reaction between azide-modified POSS (POSS-(N3)8) and alkynyl-modified PPI (PPI-Alkynyl). The hybrid POSS-(PPI)8 was with predominated left-handed helical conformation and exhibited excellent ability in the enantioselective crystallization of racemic compounds. In the meantime, heteroarm star-shaped hybrid (PEG)4-POSS-(PPI)4 was prepared by the click reaction of POSS-(N3)8 with PPI-Alkynyl and alkynyl-modified poly (ethylene glycol) (PEG-Alkynyl). The hybrid (PEG)4-POSS-(PPI)4 was amphiphilic, and it could self-assemble to form spherical micelles in aqueous solutions. 相似文献
166.
Computational characterization of the chemical step in the GTP hydrolysis by Ras‐GAP for the wild‐type and G13V mutated Ras
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Vladimir A. Mironov Maria G. Khrenova Leonora A. Lychko Alexander V Nemukhin 《Proteins》2015,83(6):1046-1053
The free energy profiles for the chemical reaction of the guanosine triphosphate hydrolysis GTP + H2O → GDP + Pi by Ras‐GAP for the wild‐type and G13V mutated Ras were computed by using molecular dynamics protocols with the QM(ab initio)/MM potentials. The results are consistent with the recent measurements of reaction kinetics in Ras‐GAP showing about two‐order reduction of the rate constant upon G13V mutation in Ras: the computed activation barrier on the free energy profile is increased by 3 kcal/mol upon the G13V replacement. The major reason for a higher energy barrier is a shift of the “arginine finger” (R789 from GAP) from the favorable position in the active site. The results of simulations provide support for the mechanism of the reference reaction according to which the Q61 side chain directly participates in chemical transformations at the proton transfer stage. Proteins 2015; 83:1046–1053. © 2015 Wiley Periodicals, Inc. 相似文献
167.
Yuping Zhang Deyu Hu Xingang Meng Qingcai Shi Pei Li Linhong Jin Kankan Zhang Baoan Song 《Chirality》2015,27(3):262-267
The stereoselective degradation of indoxacarb enriched with (+)‐S‐indoxacarb (S/R:70/30) was investigated in three typical green teas. A convenient and precise chiral method was developed and validated for measuring indoxacarb enantiomers in green tea. The developed method was based on high‐performance liquid chromatography coupled with tandem mass spectrometry using a Chiralpak IC column. The stereoselective degradation of indoxacarb enantiomers showed that the (+)‐S‐enantiomer dissipated faster than the (?)‐R‐enantiomer in all three typical tea farms. However, no enantiomerization was observed after applying pure (+)‐S‐indoxacarb. Residues on tea plant of the active ingredient (+)‐S‐indoxacarb from suspension concentrate (SC) was more persistent than that from emulsifiable concentrate (EC). Chirality 27:262–267, 2015. © 2015 Wiley Periodicals, Inc. 相似文献
168.
Enantioselective Degradation of Chiral Insecticide Dinotefuran in Greenhouse Cucumber and Soil 总被引:1,自引:0,他引:1
The enantioselective degradation behavior of the chiral insecticide dinotefuran in cucumber and soil was investigated under greenhouse conditions based on the method established with a normal‐phase high‐performance chromatography (HPLC) on a ChromegaChiral CCA column (250 × 4.6 mm, 5 µm, ES Industries). The linearity range, matrix effect, precision, and accuracy of the method were evaluated and the method was then successfully applied for the enantioselective analysis of dinotefuran in cucumber and soil. Significant enantioselectivity of degradation was observed in soil according to the results. The (+)‐dinotefuran was more persistent in soil with half‐life of 21.7 d, which is much longer than that of (–)‐dinotefuran (16.5 d). In cucumber, the (–)‐dinotefuran also tended to be preferentially degraded both in foliar and douche treatment. However, the statistical analysis indicated the enantioselectivity of degradation in cucumber was not significant. The research provides the first report concerning the enantioselective degradation of dinotefuran enantiomers and the results can be used for understanding the insect‐controlling effect and food safety evaluation. Chirality 27:137–141, 2015. © 2014 Wiley Periodicals, Inc. 相似文献
169.
Paclobutrazol, with two stereogenic centers, but gives only (2R, 3R) and (2S, 3S)‐enantiomers because of steric‐hindrance effects, is an important plant growth regulator in agriculture and horticulture. Enantioselective degradation of paclobutrazol was investigated in rat liver microsomes in vitro. The degradation kinetics and the enantiomer fraction were determined using a Lux Cellulose‐1 chiral column on a reverse‐phase liquid chromatography–tandem mass spectrometry system. The t1/2 of (2R, 3R)‐paclobutrazol is 18.60 min, while the t1/2 of (2S, 3S)‐paclobutrazol is 10.93 min. Such consequences clearly indicated that the degradation of paclobutrazol in rat liver microsomes was stereoselective and the degradation rate of (2S, 3S)‐paclobutrazol was much faster than (2R, 3R)‐paclobutrazol. In addition, significant differences between the two enantiomers were also observed in enzyme kinetic parameters. The Vmax of (2S, 3S)‐paclobutrazol was more than 2‐fold of (2R, 3R)‐paclobutrazol and the Clint of (2S, 3S)‐paclobutrazol was higher than that of (2R, 3R)‐paclobutrazol after incubation in rat liver microsomes. These results may have potential implications for better environmental and ecological risk assessment for paclobutrazol. Chirality 27:344–348, 2015. © 2015 Wiley Periodicals, Inc. 相似文献
170.
Boelo Schuur Marek Blahušiak Caecilia R. Vitasari Michal Gramblička André B. De Haan Ton J. Visser 《Chirality》2015,27(2):123-130
Enantioseparation through liquid extraction technology is an emerging field, e.g., enantioseparations of amino acids (and derivatives thereof), amino alcohols, amines, and carboxylic acids have been reported. Often, when a new selector is developed, the versatility of substrate scope is investigated. From an industrial point of view, the problem is typically approached the other way around, and for a target racemate, a selector needs to be found in order to accomplish the desired enantioseparation. This study presents such a screening approach for the separation of the enantiomers of dl ‐α‐methyl phenylglycine amide (dl ‐α‐MPGA), a model amide racemate with high industrial relevance. Chiral selectors that were reported for other classes of racemates were investigated, i.e., several macrocyclic selectors and Pd‐BINAP complexes. It appeared very challenging to obtain both high extraction yields and good enantioselectivity for most selectors, but Pd‐BINAP‐based selectors performed well, with enantioselectivities up to 7.4 with an extraction yield of the desired enantiomer of 95.8%. These high enantioselectivities were obtained using dichloromethane as solvent. Using less volatile chlorobenzene or 1‐chloropentane, reasonable selectivities of up to 1.7 were measured, making these the best alternative solvents for dichloromethane. Chirality 27:123–130, 2015. © 2014 Wiley Periodicals, Inc. 相似文献