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1.
Future pathways for combinatorial chemistry 总被引:1,自引:0,他引:1
David Brown 《Molecular diversity》1997,2(4):217-222
Summary Investment in combinatorial chemistry (combichem) in the pharmaceutical industry is being driven by the need for increased efficiency. Results from pioneers in the field have demonstrated where mixture or discrete compound synthesis is useful, and what mixture sizes and compound concentrations are appropriate. To make the techniques of combichem of general utility in drug discovery, a broad range of advances is still required. Conversion of organic chemistry to solid phase conditions is key, as are developments in linkers and resins. Library design methodology requires further development. Combinatorial biosynthesis of focused libraries of natural products holds great promise for capitalising on hardwon natural product leads. Miniaturisation of screens is required to reduce the cost of screening combinatorial libraries. Developments in the processes preceding and following synthesis are required to enable the flow of increased numbers of compounds without new bottlenecks developing. The impact of combinatorial chemistry will be greatly enhanced by synergy with ongoing parallel developments in genetic technologies, screening technologies and bioinformatics. 相似文献
2.
The acute influences of arsenic compounds on the metabolism of porphyrins and heme in various organs of rats after oral or intratracheal administration of disodium arsenate (Na2HAsO4) and gallium arsenide (GaAs) were examined and compared. For the oral administration experiments, 21 or 84 mg of Na2HAsO4, or 2 or 4 g of GaAs, per cm3 saline per kg body weight of each animal was administered to Jcl: Wistar male rats and the organs were removed after exsanguination from the vein of the right axilla under anesthesia with ether, 16 h after administration. In the case of intratracheal administration, rats given 8.2 or 16.4 mg of Na2HAsO4, or 0.2 or 0.4 g GaAs per cm3 saline per kg body weight were examined under the same experimental conditions as for the administration route. Increase in the body weight of rats was suppressed after intratracheal administration of the two arsenic compounds. In these rats the hematocrit value increased significantly. These changes were not shown by the orally administered rats. Elevation in δ-aminolevulinate synthase (ALA-S, EC 2.3.1.37) activity in erythroblasts by Na2HAsO4 was much higher after intratracheal administration than after oral administration. Suppression in the activities of δ-aminolevulinate dehydratase (ALA-D, EC 4.2.1.24) and porphobilinogen deaminase (PBG-D, EC 4.3.1.8) in peripheral erythrocytes by Na2HAsO4 and GaAs were stronger by intratracheal administration than by the oral route. Influences of GaAs on the activity of PBG-D in rat liver were shown to be more effective by oral administration than by the intratracheal route. Oral administration of Na2HAsO4 and GaAs had a stronger suppression effect on the activities of ALA-D and PBG-D in rat kidney. It seems from these results that the different extents of the influence of arsenic compounds might depend on the routes of intake. 相似文献
3.
A new, high performance liquid chromatography method has been developed for the separation of monovinyl- and divinyl-protochlorophyllides, using commercially available, C30 reverse phase column and isocratic elution. This method can be used both for analytical applications and preparative scale purification of monovinyl- and divinyl-protochlorophyllides using the same column where submilimolar concentrations of the crude protochlorophyllide extract can be separated in one run. The purity of the obtained protochlorophyllides was demonstrated by spectroscopic methods, as well by the formation of aggregates in toluene. 相似文献
4.
由肉桂酸生物合成L-苯丙氨酸 总被引:4,自引:0,他引:4
本文评述了L-苯丙氮酸的各种合成路线、国内外的研究现状及工业化情况,重点讨论了由肉桂酸和氨生物合成L-苯丙氨酸的路线,提出了在国内进一步工作的建议。 相似文献
5.
Kaloustian J Pauli A-M Lechene de la Porte P Lafont H Portugal H 《Journal of Thermal Analysis and Calorimetry》2003,71(2):341-351
Cholesterol constitutes the major component of most gallstones. It was identified and determined, in gallstones, issued from
eleven patients, by thermal analysis: differential scanning calorimetry (DSC), with the use of the melting temperature and
enthalpy, thermogravimetry (TG), with the mass loss of water. Anhydrous cholesterol (ChA) was characterized by two endothermic
peaks (polymorphic, melting) and cholesterol monohydrate (ChH) by two endothermic peaks (dehydration, melting), too. Cha needle
and Chh plate crystals were observed under polarizing light microscopy. The numerous stones obtained from nine patients were
cholesterol stones: the ChA was higher 45 and lower 96%. ChH was present in stones of three patients.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
6.
Allais C. Keller G. Lesieur P Ollivon M. Artzner F. 《Journal of Thermal Analysis and Calorimetry》2003,74(3):723-728
Polymorphism of trilaurin mixed with 4% of cholesterol was studied with a setup coupling calorimetry and phase characterisation
by in-situ X-ray diffraction (Microcalix). Four polymorphic forms were identified. Monotropic and enantiotropic transitions
were identified from the reconstruction of Gibbs free energy diagram which allows the control of trilaurin polymorphism.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
7.
《Arabian Journal of Chemistry》2022,15(11):104272
Yinlan lipid regulatory capsule (YL) is a composite traditional Chinese medicine (TCM) new drug to alleviate hyperlipidemia, while its therapeutic mechanism in vivo was not clarified with nontargeted metabolomics investigation. An animal model was established in rats fed a high-fat diet, and their body weights, body mass index (BMI) and blood cholesterol levels were measured. Serum, liver and kidney tissue samples were also extracted for PXR-CYP3A4-ABCB1-FXR signaling pathway research using PCR and UHPLC–MS. The obtained plasma samples were analyzed by UHPLC-Q-TOF-MS metabolomic investigation, which revealed PXR-CYP3A4-related metabolites and changes induced by YL. Finally, the key metabolites were chosen as index components, and their levels in the serum, liver, small intestine and bile were used for simultaneous UHPLC–MS-MS determination. The results indicated that YL was effective in rebalancing blood TG and TC levels (compared to controls). With respect to the PXR-CYP3A4-ABCB1 pathway, as a result of YL’s effect, gene expression or activity of the two targets decreased significantly in both the liver and kidney. The same trend was observed in the serum samples mentioned above. Metabolomics screening and data revealed that 44 metabolites can be regarded as biomarkers related to hyperlipidemia, fatty acids synthesis, and body energy consumption, as well as synthesis, transportation and exertion of cholesterol. YL’s treatment focused on 26 of them, primarily bile acids, indicating that the antihyperlipidemic effect of this drug lies in its inhibitory activity of cholesterol metabolism. Subsequent analysis of those in vivo components revealed that significant increases (compared to the model group) occurred in the blood, liver, small intestine and bile in groups that received medium and high doses of YL (while the low dose was relatively unchanged). Those target components exhibit a close relationship with PXR and/or CYP3A4. The use of YL repressed PXR expression and subsequently decreased CYP3A4 activity. As a result, synthesis of related bile acids increased, while cholesterol levels decreased, consequently leading to the attenuation of hyperlipidemia. This study comprehensively investigated the antihyperlipidemia mechanism of YL based on its repression of PXR-CYP3A4 activity and related metabolite yield, establishing an accurate method for evaluating the therapeutic effect of YL. 相似文献
8.
Labeling experiments using several deuterated lipids were pursued to study the biosynthesis of macrocyclic isoprenoidal lipids of thermophilic methanogenic archaea, Methanothermobacter thermautotrophicus. The isopropylidene terminal of geranylgeranyl group of monomeric precursor appeared to be important for the CC bond formation at the hydrophobic end in the macrocyclic lipids. A mechanism involving a radical trigger at the allylic methyl group is proposed for this CC bond formation. 相似文献
9.
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