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41.
Rosa M. Claramunt Concepcin Lpez Carlos Prez-Medina Marta Prez-Torralba Jos Elguero Germaine Escames Darío Acua-Castroviejo 《Bioorganic & medicinal chemistry》2009,17(17):776-6187
In order to find new compounds with neuroprotective activity and NOS-I/NOS-II selectivity, we have designed, synthesized, and characterized 14 new NOS inhibitors with an indazole structure. The first group corresponds to 4,5,6,7-tetrahydroindazoles (4–8), the second to the N-methyl derivatives (9–12) of 7-nitro-1H-indazole (1) and 3-bromo-7-nitro-1H-indazole (2), and the latter to 4,5,6,7-tetrafluoroindazoles (13–17). Compound 13 (4,5,6,7-tetrafluoro-3-methyl-1H-indazole) inhibited NOS-I by 63% and NOS-II by 83%. Interestingly, compound 16 (4,5,6,7-tetrafluoro-3-perfluorophenyl-1H-indazole) inhibited NOS-II activity by 80%, but it did not affect to NOS-I activity. Structural comparison between these new indazoles further supports the importance of the aromatic indazole skeleton for NOS inhibition and indicate that bulky groups or N-methylation of 1 and 2 diminish their effect on NOS activity. The fluorination of the aromatic ring increased the inhibitory potency and NOS-II selectivity, suggesting that this is a promising strategy for NOS selective inhibitors. 相似文献
42.
López LC Escames G Tapias V Utrilla P León J Acuña-Castroviejo D 《The international journal of biochemistry & cell biology》2006,38(2):267-278
Sepsis provokes an induction of inducible nitric oxide synthase (iNOS) and melatonin down-regulates its expression and activity. Looking for an inducible mtNOS isoform, we induced sepsis by cecal ligation and puncture in both normal and iNOS knockout mice and studied the changes in mtNOS activity. We also studied the effects of mtNOS induction in mitochondrial function, and the role of melatonin against induced mtNOS and mitochondrial dysfunction. The activity of mtNOS and nitrite levels significantly increased after sepsis in iNOS+/+ mice. These animals showed a significant inhibition of the respiratory chain activity and an increase in mitochondrial oxidative stress, reflected in the disulfide/glutathione ratio, glutathione redox cycling enzymes activity and lipid peroxidation levels. Interestingly, mtNOS activity remained unchanged in iNOS-/- septic mice, and mitochondria of these animals were unaffected by sepsis. Melatonin administration to iNOS+/+ mice counteracted mtNOS induction and respiratory chain failure, restoring the redox status. The results support the existence of an inducible mtNOS that is likely coded by the same gene as iNOS. The results also suggest that sepsis-induced mtNOS is responsible for the increase of mitochondrial impairment due to oxidative stress in sepsis, perhaps due to the high production of NO. Melatonin treatment prevents mitochondrial failure at the same extend as the lack of iNOS gene. 相似文献
43.
The diagnoses of summer or winter hypertension in one and the same person can depend upon the clock hour of measurement. 相似文献
44.
Heme catalases are homotetrameric enzymes with a highly conserved complex quaternary structure, and their functional role is still not well understood. Proteus mirabilis catalase (PMC), a heme enzyme belonging to the family of NADPH-binding catalases, was efficiently overexpressed in E. coli. The recombinant catalase (rec PMC) was deficient in heme with one-third heme and two-thirds protoporphyrin IX as determined by mass spectrometry and chemical methods. This ratio was influenced by the expression conditions, but the enzyme-specific activity calculated relative to the heme content remained unchanged. The crystal structure of rec PMC was solved to a resolution of 2.0 A, the highest resolution obtained to date with PMC. The overall structure was quite similar to that of wild-type PMC, and it is surprising that the absence of iron had no effect on the structure of the active site. Met 53 close to the essential His 54 was found less oxidized in rec PMC than in the wild-type enzyme. An acetate anion was modeled in an anionic pocket, away from the heme group but important for the enzymatic reaction. An alternate conformation observed for Arg 99 could play a role in the formation of the H-bond network connecting two symmetrical subunits of the tetramer. 相似文献
45.
46.
Jean-Philippe Rameau Germaine Robinet Jean Devillers 《Journal of molecular modeling》1998,4(12):405-416
A new type of carbon atom has been included in the MM2 force field when it is part of a carbonyl group cross-conjugated in a heterocyclic molecule. This carbon atom is fully included in the π system calculation. New stretching parameters for the C=O bond have been estimated by a statistical process from X-ray molecular structures recorded in the Cambridge Structural Database System. The proposed parameters have been found appropriate for compounds in which the atoms adjacent to the carbonyl are a carbon and a heteroatom i.e. mainly for the α-pyrone ring and the conjugated "lactams". They are inappropriate for carbonates and oxazo-ones but should be valid for quinones provided that they are not involved in a charge transfer complex. The mean unsigned deviation for 111 bond lengths (89 cyclic molecules) is 0.01Å but the maximum deviation can reach ± 0.03Å. Part of the observed dispersion could be the result of the variation of the effective dielectric constant D from one crystal to another. 相似文献
47.
Eric Provost Germaine Riviere Maurice Roux E. David Morgan Anne G. Bagneres 《Insect biochemistry and molecular biology》1993,23(8):945-957
The cuticular hydrocarbons of foraging workers of the ant Leptothorax lichtensteini have been identified by gas chromatography-mass spectrometry. Characterization of these compounds at regular intervals, by gas chromatography, has shown a change with time in the relative proportions of some of the hydrocarbons: n-hexacosane, 4-methylhexacosane, 4-methyloctacosane, 3-methylnoncosane. Some of which constitute a part of the colony signature. These changes occur in a synchronous manner, and in the same way for all the individuals of a colony tested at the same time. The changes also appear in queenless colonies; nevertheless, the presence of a queen seems to accelerate the change over the course of 1 yr. Certain hypotheses are formulated as to the mode of regulation of the synthesis of cuticular hydrocarbons responsible for these changes with time and as to the role played by the queen in this regulation. The implications of such a dynamic system for the process of nestmate recognition are discussed. 相似文献
48.
Marie Germaine T. Matchide Saw Yu Yu Hnin Yves M. Mba Nguekeu Elodie Gaële Matheuda Josker Nghokeng Gaetan T. Tabakam Raymonde A. Dzatie Djoumbissie Silvère Augustin Ngouela Yuan-E Lee Mathieu Tene Hiroyuki Morita Maurice Ducret Awouafack 《化学与生物多样性》2023,20(9):e202301127
A new fructofuranoside glycerol, dryoptkirbioside ( 1 ), along with thirteen known compounds ( 2 - 14 ), was isolated from the MeOH extract of Dryopteris kirbi rhizomes by silica gel column chromatography, Sephadex LH-20 column chromatography, and semipreparative HPLC. The structure of the new compound was determined by analyses of its spectroscopic data including nuclear magnetic resonance (NMR), and high-resolution electrospray ionisation mass spectrometry (HR-ESI-MS) and chemical conversions. The hexane-soluble portion and the EAFA fraction showed strong activities against lung (A549), breast (MCF-7), and cervical (HeLa) human cancer cell lines (IC50 values ranging from 4.0 to 8.8 μg/mL). Aspidinol P ( 5 ) and aspidinol B ( 6 ) exhibited moderate to low cytotoxicity on the three cell lines (IC50 values ranging from 20.4 to 58.7 μM). The MeOH extract and hexane-soluble portion had excellent activities against Staphylococcus aureus and Bacillus subtilis (MICs 11.7 and 23.4 μg/mL), whereas the AcOEt- and BuOH-soluble portions were significantly active on S. aureus (MICs 46.9 and 93.8 μg/mL). The main fractions EAFB, EAFC and nBFB displayed excellent activity against S. aureus (MICs 11.7 and 23.4 μg/mL). Aspidinol B ( 6 ) had significant activity, while aspidinol P ( 5 ) was moderately active against S. aureus and B. subtilis (MICs 42.0 and 89.5 μM). 相似文献
49.
Donald A. Bryant Germaine Cohen-Bazire Alexander N. Glazer 《Archives of microbiology》1981,129(3):190-198
The biliproteins of the unicellular, thylakoid-less cyanobacterium Gleobacter violaceus were resolved by chromatography on hydroxylapatite and DEAE-cellulose into five components: phycoerythrin I and II, phycocyanin I and II, and allophycocyanin. Allophycocyanin B was not detected. Three of these components, phycoerythrin II, phycocyanin II, and allophycocyanin, were purified to homogeneity. Phycoerythrin II crystallized as hexagonal prisms. G. violaceus allophycocyanin crystallized as thin plates; unter similar conditions other cyanobacterial allophycocyanins crystallize as needles. The biliproteins in the phycoerythrin I and phycocyanin I components were present in polydisperse, high molecular weight aggregates, which may represent incompletely dissociated substructures of the phycobilisome.Both phycoerythrin components from G. violaceus carry phycoerythrobilin and phycourbilin groups in the ratio of 6:1. Separation of the and subunits of these biliproteins revealed that the phycoerythrobilins were equally distributed between the two subunits, and that the subunit alone carried the phycourobilin. These phycoerythrins are the first cyanobacterial phycobiliproteins found to carry a phycourobilin prosthetic group.Abbreviations used PE
poycoerythrin
- PC
phycocyanin
- AP
allophycocyanin
- SDS
sodium dodecyl sulfate
- PAGE
polyacrylamide gel electrophoresis
- B
Bangiophycean
- R
Rhodophytan
- C
Cyanobacterial 相似文献
50.
Acidic proteins from many biogenic minerals are implicated in directing the formation of crystal polymorphs and morphologies. We characterize the first extremely acidic proteins purified from biomineralized aragonite. These abalone nacre proteins are two variants of 8.7 and 7.8 kDa designated AP8 (for aragonite proteins of approximately 8 kDa). The AP8 proteins have compositions dominated by Asx ( approximately 35 mol %) and Gly ( approximately 40 mol %) residues, suggesting that their structures have high Ca(2+)-binding capacity and backbone flexibility. The growth of asymmetrically rounded CaCO(3) crystals in the presence of AP8 reveals that both proteins preferentially interact with specific locations on the crystal surface. In contrast, CaCO(3) crystals grown with nacre proteins depleted of AP8 retain the morphology of unmodified calcite rhombohedra. Our observations thus identify sites of protein-mineral interaction and provide evidence to support the long-standing theory that acidic proteins are more effective crystal-modulators than other proteins from the same biomineralized material. 相似文献