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91.
Seko T Kato M Kohno H Ono S Hashimura K Takenobu Y Takimizu H Nakai K Maegawa H Katsube N Toda M 《Bioorganic & medicinal chemistry letters》2002,12(17):2267-2269
This study was performed to determine the structure-activity relationships (SAR) of L-cysteine based N-type calcium channel blockers. Basic nitrogen was introduced into the C-terminal lipophilic moiety of L-cysteine with a view toward improvement of its physicochemical properties. L-Cysteine derivative 9 was found to be a potent and selective N-type calcium channel blocker with IC(50) of 0.33 microM in calcium influx assay using IMR-32 cells and was 15-fold selective for N-type calcium channels over L-type channels. Compound 9 showed improved oral analgesic efficacy in the rat formalin induced pain model and the rat chronic constriction injury (CCI) model, which is one of the most reliable models of chronic neuropathic pain, without any significant effect on blood pressure or neurological behavior. 相似文献
92.
Yoshiizumi K Nakajima F Dobashi R Nishimura N Ikeda S 《Bioorganic & medicinal chemistry》2002,10(8):2445-2460
Scavenger receptors have been proven to be implicated in the formation of atherosclerotic lesions. A series of novel derivatives of sulfatides were synthesized, and their inhibitory activities against incorporation of DiI-acetyl-LDL into macrophages were evaluated in order to clarify the structure-activity relationships of sulfatides as a scavenger receptor inhibitor and find out novel inhibitors with synthetic easiness. The chemical modification of the substructures of sulfatides led to the establishment of the following structure-activity relationships; (1) the ceramide moiety can be replaced with another structure bearing two long chains, (2) the galactose moiety can be replaced with another structure or be deleted without a large decrease in the inhibitory activity, (3) the sulfate moiety was crucial, and it was the most preferable functional group for a potent inhibitory activity. The inhibitory activity of (S)-2-octadecanoylamino-2-tetradecylcarbamoyl)ethyl sulfate sodium salt (3a) against incorporation of DiI-acetyl-LDL into macrophages was proven to be based on the inhibition against the binding of acetyl-LDL to the surface of macrophages. We discovered novel scavenger receptor inhibitors with synthetic easiness, such as (S)-2-octadecanoylamino-2-(tetradecylcarbamoyl)ethyl sulfate sodium salt (3a) and 2-octadecanoylamino-1-(octadecanoylaminomethyl)ethyl sulfate sodium salt (13q). 相似文献
93.
Deligeer Fukunaga R Kataoka K Yamaguchi K Kobayashi K Tagawa S Suzuki S 《Journal of inorganic biochemistry》2002,91(1):132-138
The Cu-containing nitrite reductase from Hyphomicrobium denitrificans (HydNIR) has been spectroscopically and functionally characterized. The visible absorption spectrum implies that the enzyme has two type 1 Cu ions in one subunit (ca. 50 kDa). The electron paramagnetic resonance (EPR) spectrum of HydNIR is simulated assuming the sum of three distinct S = 1/2 systems: two type 1 Cu signals (axial and rhombic symmetries) and one type 2 Cu signal. The intramolecular electron transfer reaction from the type 1 Cu to the type 2 Cu at pH 6.0 does not occur in the absence of nitrite, but a very slow electron transfer reaction is observed in the presence of nitrite. The apparent first-order rate constants for the intramolecular electron transfer reactions (k(ET(intra))) in the presence of nitrite and also the apparent catalytic rate constants (k(cat)) of HydNIR decrease gradually with increasing pH in the range of pH 4.5-7.5. These pH profiles are substantially similar to each other, suggesting that the intramolecular electron transfer process is linked to the subsequent nitrite reduction process. 相似文献
94.
Asexual worms of an exclusively fissiparous strain (the OH strain) of the planarian Dugesia ryukyuensis keep developing hermaphroditic reproductive organs and eventually undergo sexual reproduction instead of asexual reproduction, namely fission, if they are fed with sexually mature worms of an exclusively oviparous planarian, Bdellocephala brunnea, suggesting that the sexually mature worms has a sexualizing substance(s). The fully sexualized worms no longer need the feeding on sexual worms to maintain the sexuality. Here, we demonstrate that the sexualized worms produce enough of their own sexualizing substance similar to that contained in B. brunnea. In case of surgical ablation of the sexualized worms, the fragments with sexual organs regenerate to become sexual, while those without sexual organs, namely head fragments, regenerate to return to the asexual state. The asexual regenerants from the sexualized worms are also fully sexualized by being fed with B. brunnea. Additionally, it was reported that head region in sexually mature worms lacks the putative sexualizing substance necessary for complete sexualization (Sakurai, 1981). These results suggest that the fragments without sexual organ lack enough of an amount of the putative sexualizing substance and the sexuality is maintained by the sexualizing substance contained in the sexualized worms. 相似文献
95.
Asexual individuals in a fissiparous clone of the planarian Dugesia ryukyuensis develop hermaphroditic sexual organs and eventually undergo sexual reproduction instead of asexual reproduction if they are fed with the adults of Bdellocephala brunnea, an oviparous planaria. The experimental sexualization means that the adults of B. brunnea contain a putative sexualizing substance(s), which is the first candidate for the chemical(s) responsible for switching from asexual to sexual reproduction in metazoans. In the present study, the feeding experiment over two consecutive years revealed that the experimental sexualization has seasonal changes. In summer, the asexual individuals were not fully sexualized, though they developed a pair of ovaries. The developing ovaries degenerate if the feeding is stopped. On the contrary, in winter, they developed all the sexual organs. The sexual organs keep developing even if the feeding is stopped after a certain critical point named the point-of-no-return. It was demonstrated that the extreme difference of the sexualization was attributed to the seasonal change of the quality and/or quantity of the sexualizing substance contained in B. brunnea, as well as the minor change of the susceptibility to the sexualizing substance in the asexual individuals. On the other hand, the histological research of B. brunnea revealed that the degree of the maturation of the sexual organs varied extremely through a year. Taking these results into account, we suggest that the production of the sexualizing substance has no direct relation to any particular mature sexual organs. 相似文献
96.
For randomly selected 50 villages in Bangladesh, an interview survey with a structured questionnaire was conducted to reveal their perception on the environmental, health and economic conditions at present and for the past 10-year change. The eight following items were analyzed in this paper: air pollution and water pollution, which represent environmental conditions with close relation to health conditions, soil degradation and deforestation, which represent environmental conditions with close relation to economic conditions, epidemic diseases and malnutrition, which represent health conditions, and poverty and jobless, which represent economic conditions. Among the 50 villages, deforestation was most frequently perceived serious at present and worsened in the past 10 years. Of the remaining seven items, those related to economic conditions were more seriously perceived than those related to health and environmental conditions. As revealed by the cluster analysis for the inter-item relations, epidemic diseases, which formed the same cluster with the environmental items, were recognized less serious whereas malnutrition, which formed the same cluster with the economic items, was recognized more serious. These findings are useful not only for rural development programs but also for mitigation programs toward health and environmental hazards in Bangladesh. 相似文献
97.
Momose Y Honda T Inagaki M Shimizu K Irie K Nakanishi H Takai Y 《Biochemical and biophysical research communications》2002,292(1):45-49
We investigated whether and how rat liver thioredoxin reductase spares alpha-tocopherol in biomembranes. Purified hydroperoxides of beta-linoleoyl-gamma-palmitoylphosphatidylcholine were decreased 35% by treatment with thioredoxin reductase and 54% by thioredoxin reductase plus E. coli thioredoxin. Thioredoxin reductase also halved the amount of hydroperoxides that had been formed during photoperoxidation of liposomes composed of beta-linoleoyl-gamma-palmitoylphosphatidylcholine, and of emulsions of both cholesterol and cholesteryl linolenate. In erythrocyte ghosts, thioredoxin reductase spared alpha-tocopherol from oxidation by both soybean lipoxygenase and ferricyanide. Thioredoxin reductase also decreased F(2)-isoprostanes in ghosts oxidized by ferricyanide, suggesting that its ability to spare alpha-tocopherol relates to reduction of lipid hydroperoxides. 相似文献
98.
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100.
Schizophyllan (SPG), a beta-1,3-glucan polysaccharide which is known to form macromolecular complexes with certain polynucleotides, was modified by a reductive amination method with alpha-amino acids (Arg, Lys, and Ser). The thermal stability of the complexes as estimated by T(m) was enhanced in SPG-Arg and SPG-Lys conjugates which have pI values higher than the pH of the medium (8.0). The T(m) shift increased with the increase in the percentage of alpha-amino acid introduced and the highest T(m) values attained were 64 degrees C for SPG-Arg conjugate and 62 degrees C for SPG-Lys conjugate, which are higher by 13 and 11 degrees C, respectively, than those of the unmodified SPG+poly(C) complex. In the SPG-Ser conjugate with a pI lower than the medium pH (8.0), the T(m) values decreased with an increase in the percentage of Ser. Formation of the macromolecular complex was no longer detected above 13.2% Ser. The findings indicate that the T(m) values are easily controllable by the type and percentage of the introduced alpha-amino acids. We believe, therefore, that the present conjugates, consisting of naturally originated SPG and alpha-amino acids, provide an important lead for developing nontoxic artificial vectors and to control the affinity with polynucleotides in response to medium pH and temperature. 相似文献