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排序方式: 共有153条查询结果,搜索用时 15 毫秒
101.
Jean-Guy Boiteau Gilles Ouvry Jean-Marie Arlabosse Stéphanie Astri Audrey Beillard Yushma Bhurruth-Alcor Laetitia Bonnary Claire Bouix-Peter Karine Bouquet Marilyne Bourotte Isabelle Cardinaud Catherine Comino Benoît Deprez Denis Duvert Angélique Féret Feriel Hacini-Rachinel Craig S. Harris Anne-Pascale Luzy Laurent F. Hennequin 《Bioorganic & medicinal chemistry》2018,26(4):945-956
Targeting the TNFα pathway is a validated approach to the treatment of psoriasis. In this pathway, TACE stands out as a druggable target and has been the focus of in-house research programs. In this article, we present the discovery of clinical candidate 26a. Starting from hits plagued with poor solubility or genotoxicity, 26a was identified through thorough multiparameter optimisation. Showing robust in vivo activity in an oxazolone-mediated inflammation model, the compound was selected for development. Following a polymorph screen, the hydrochloride salt was selected and the synthesis was efficiently developed to yield the API in 47% overall yield. 相似文献
102.
Berrin JG Pierrugues O Brutesco C Alonso B Montillet JL Roby D Kazmaier M 《Molecular genetics and genomics : MGG》2005,273(1):10-19
A novel Arabidopsis thaliana gene (AtNADK-1) was identified based on its response to radiation and oxidative stress. Levels of AtNADK-1 mRNA increase eight-fold following exposure to ionising radiation and are enhanced three-fold by treatment with hydrogen peroxide. The gene also appears to be differentially regulated during compatible and incompatible plant-pathogen interactions in response to Pseudomonas syringae pv. tomato. The full-length AtNADK-1 cDNA encodes a 58-kDa protein that shows high sequence homology to the recently defined family of NAD(H) kinases. Recombinant AtNADK-1 utilises ATP to phosphorylate both NAD and NADH, showing a two-fold preference for NADH. Using reverse genetics, we demonstrate that AtNADK-1 deficient plants display enhanced sensitivity to gamma irradiation and to paraquat-induced oxidative stress. Our results indicate that this novel NAD(H) kinase may contribute to the maintenance of redox status in Arabidopsis thaliana. 相似文献
103.
Martin B Possémé F Le Barbier C Carreaux F Carboni B Seiler N Moulinoux JP Delcros JG 《Bioorganic & medicinal chemistry》2002,10(9):2863-2871
Polyamine vectors are attractive for tumor targeting. We envisaged (Z)-1,4-diamino-2-butene (Z-DAB), an unsaturated analogue of putrescine as vector of (10)B, (18)F and (131)I for boron neutron capture therapy (BNCT), and tumor imaging by positron emission tomography or scintigraphy respectively. In the present work, the synthesis and characterization of new derivatives of Z-DAB were reported. Z-DAB was actively transported in cells via the polyamine transport system and converted into the spermidine analogue.(E)-2-iodo-1,4-diamino-2-butene (E-I-DAB) was not taken up by the polyamine transport system and may not be suitable for tumor imaging. In contrast, (Z)-2-[4-(5,5-dimethyl-dioxaborinan-2-yl)phenyl]methyl-1,4-diamino-2-butene (Z-4-Bbz-DAB) was a substrate of the transport system and allowed significant boron accumulation in 3LL cells. Its potential in BNCT will be evaluated. 相似文献
104.
105.
Body length variation within multi-species fish shoals: the effects of shoal size and number of species 总被引:2,自引:0,他引:2
Theory predicts that selection should favour phenotypic homogeneity in fish shoals, and field studies have indeed confirmed
that variation in body length within fish shoals is significantly lower than expected from a random distribution of fish among
shoals. We investigated the extent to which variation in fish body length within shoals is determined by the shoal mean of
body length, the number of species in a shoal, and the overall shoal size. We collected 34 fish shoals, ranging in size from
6 to 776 individuals, from the littoral zone of a Canadian lake. Shoals consisted of up to four different species, with multi-species
shoals being larger and more frequent than single-species ones. The strongest determinant of body length variation within
shoals was the shoal mean of body length, followed by the number of fish species in a shoal; i.e. multi-species shoals were
less size-assorted than single-species ones. A more detailed analysis showed that the higher body length variation observed
in multi-species shoals was due to increased body length variation both within and between component species. Shoal size had
no significant effect on body length variation within shoals. Potential explanations of the positive relationship between
body length variation and the number of species in a shoal are suggested. The implications of the above results for the evolution
of multi-species shoals are discussed.
Received: 6 May 1997 / Accepted: 14 October 1997 相似文献
106.
107.
Berrin JG Ajandouz el H Georis J Arnaut F Juge N 《Applied microbiology and biotechnology》2007,74(5):1001-1010
Two genes encoding family 11 endo-(1,4)-β-xylanases from Penicillium griseofulvum (PgXynA) and Penicillium funiculosum (PfXynC) were heterologously expressed in Escherichia coli as glutathione S-transferase fusion proteins, and the recombinant enzymes were purified after affinity chromatography and
proteolysis. PgXynA and PfXynC were identical to their native counterparts in terms of molecular mass, pI, N-terminal sequence,
optimum pH, and enzymatic activity towards arabinoxylan. Further investigation of the rate and pattern of hydrolysis of PgXynA
and PfXynC on wheat soluble arabinoxylan showed the predominant production of xylotriose and xylobiose as end products. The
initial rate data from the hydrolysis of short xylo-oligosaccharides indicated that the catalytic efficiency increased with
increasing chain length (n) of oligomer up to n = 6, suggesting that the specificity region of both Penicillium xylanases spans about six xylose units. In contrast to PfXynC, PgXynA was found insensitive to the wheat xylanase inhibitor
protein XIP-I. 相似文献
108.
The emergence and early developments of life are considered from the point of view that contingent events that inevitably marked evolution were accompanied by deterministic driving forces governing the selection between different alternatives. Accordingly, potential energy sources are considered for their propensity to induce self-organization within the scope of the chemical approach to the origin of life. Requirements in terms of quality of energy locate thermal or photochemical activation in the atmosphere as highly likely processes for the formation of activated low-molecular weight organic compounds prone to induce biomolecular self-organization through their ability to deliver quanta of energy matching the needs of early biochemical pathways or the reproduction of self-replicating entities. These lines of reasoning suggest the existence of a direct connection between the free energy content of intermediates of early pathways and the quanta of energy delivered by available sources of energy. 相似文献
109.
Fleury A Mathieu AP Ducharme L Hales DB LeHoux JG 《The Journal of steroid biochemistry and molecular biology》2004,91(4-5):259-271
In order to study the effect of phosphorylation on the function of the steroidogenic acute regulatory protein (StAR), 10 putative phosphorylation sites were mutated in the hamster StAR. In pcDNA3.1-StAR transfected COS-1 cells, decreases in basal activity were found for the mutants S55A, S185A and S194A. Substitution of S185 by D or E to mimic phosphorylation resulted in decreased activity for all mutants; we concluded that S185 was not a phosphorylation site and we hypothesized that mutations on S185 created StAR conformational changes resulting in a decrease in its binding affinity for cholesterol. In contrast, the mutation S194D resulted in an increase in StAR activity. We have calculated the relative rate of pregnenolone formation (App. Vmax) in transfected COS-1 cells with wild type (WT) and mutant StAR-pcDNA3.1 under control and (Bu)2-cAMP stimulation. The App. Vmax values refer to the rate of cholesterol transported and metabolized by the cytochrome P450scc enzyme present in the inner mitochondrial membrane. The App. Vmax was 1.61 ± 0.28 for control (Ctr) WT StAR and this value was significantly increased to 4.72 ± 0.09 for (Bu)2-cAMP stimulated preparations. App. Vmax of 5.53 (Ctr) and 4.82 ((Bu)2-cAMP) found for S194D StAR preparations were similar to that of the WT StAR stimulated preparations. At equal StAR quantity, an anti-phospho-(S/T) PKA substrate antibody revealed four times more phospho-(S/T) in (Bu)2-cAMP than in control preparations. The intensity of phosphorylated bands was decreased for the S55A, S56A and S194A mutants and it was completely abolished for the S55A/S56A/S194A mutant. StAR activity of control and stimulated preparations were diminished by 73 and 72% for the mutant S194A compared to 77 and 83% for the mutant S55A/S56A/S194A. The remaining activity appears to be independent of phosphorylation at PKA sites and could be due to the intrinsic activity of non-phosphorylated StAR or to an artefact due to the pharmacological quantity of StAR expressed in COS-1. In conclusion we have shown that (Bu)2-cAMP provokes an augmentation of both the quantity and activity of StAR, and that an enhancement in StAR phosphorylation increases its activity. The increased quantity of StAR upon (Bu)2-cAMP stimulation could be due to an augmentation of its mRNA or protein synthesis stability, or both; this is yet to be determined. 相似文献
110.
Wind as an abiotic factor of Colorado potato beetle (Coleoptera: Chrysomelidae) flight take-off activity under field conditions 总被引:1,自引:0,他引:1
The flight take-off activity of Colorado potato beetles, Leptinotarsa decemlineata (Say) (Coleoptera: Chrysomelidae), was significantly higher at a landscape-protected than at semiexposed and exposed sites in a 2-yr field study. In both years, mean daylight temperature, solar radiation, and relative humidity were generally similar at all sites, but wind speed was lower at the protected site than at the exposed sites. Results suggest that wind was the limiting abiotic factor for flight take-off at the exposed site. Caged beetles exposed to constant wind speeds of 3.4, 4.7, and 7.0 m/s showed a significant corresponding decrease in number of flight take-off. There was no cumulative effect of wind exposure on the readiness of the beetles to fly, suggesting that wind acts as a physical barrier to flight take-off. It should be possible to reduce Colorado potato beetle flight dispersal by selecting fields most exposed to wind over landscape-protected fields when rotating potato, Solanum tuberosum L., crops. 相似文献