全文获取类型
收费全文 | 533篇 |
免费 | 29篇 |
出版年
2023年 | 1篇 |
2022年 | 8篇 |
2021年 | 13篇 |
2020年 | 6篇 |
2019年 | 2篇 |
2018年 | 11篇 |
2017年 | 8篇 |
2016年 | 13篇 |
2015年 | 27篇 |
2014年 | 29篇 |
2013年 | 50篇 |
2012年 | 61篇 |
2011年 | 52篇 |
2010年 | 29篇 |
2009年 | 37篇 |
2008年 | 26篇 |
2007年 | 15篇 |
2006年 | 29篇 |
2005年 | 23篇 |
2004年 | 24篇 |
2003年 | 20篇 |
2002年 | 16篇 |
2001年 | 4篇 |
2000年 | 2篇 |
1999年 | 2篇 |
1998年 | 6篇 |
1997年 | 5篇 |
1996年 | 3篇 |
1995年 | 3篇 |
1994年 | 6篇 |
1993年 | 4篇 |
1992年 | 2篇 |
1989年 | 4篇 |
1988年 | 1篇 |
1986年 | 1篇 |
1985年 | 1篇 |
1983年 | 1篇 |
1982年 | 4篇 |
1981年 | 2篇 |
1980年 | 2篇 |
1979年 | 2篇 |
1975年 | 1篇 |
1971年 | 1篇 |
1963年 | 1篇 |
1961年 | 1篇 |
1960年 | 1篇 |
1957年 | 1篇 |
1951年 | 1篇 |
排序方式: 共有562条查询结果,搜索用时 15 毫秒
1.
Elisabet Johansson Lars Hedbys Per-Olof Larsson Klaus Mosbach Alf Gunnarsson Sigfrid Svensson 《Biotechnology letters》1986,8(6):421-424
Summary Three naturally occurring isomers of the disaccharideO--d-mannosyl-d-mannoside were synthesized by reversing the hydrolytic activity of jack bean -mannosidase at 75°C in a very high concentration of mannose. Higher oligosaccharides were also obtained at the later stages of the reaction. The maximum total yield of disaccharides was 37% (w/w) based on the total amount of saccharides. 相似文献
2.
Empis borealisfemales form swarms, and males carrying a nuptial gift come to swarms to mate. Males either mated with one of the females (accepted swarms) or left swarms without mating (refused swarms). Males mated with the younger (low wing-wear) and relatively larger females in accepted swarms. They seemed to be able to judge the relative size of the females but to ignore their absolute size. Visiting males stayed shorter in accepted swarms as female size variation increased. This probably reflects their greater ease in choosing a mate among females of relatively different sizes. Females in accepted swarms tended to be larger and to have less worn wings than females in rejected swarms. 相似文献
3.
Mario H.J. Vogt Elisabet H. Stet Ronney A. De Abreu Jos P.M. Bökkerink Lambert H.J. Lambooy Frans J.M. Trijbels 《生物化学与生物物理学报:疾病的分子基础》1993,1181(2):189-194
The importance of methyl-thioIMP (Me-tIMP) formation for methylmercaptopurine ribonucleoside (Me-MPR) cytotoxicity was studied in Molt F4 cells. Cytotoxicity of Me-MPR is caused by Me-tIMP formation with concomitant inhibition of purine de novo synthesis. Inhibition of purine de novo synthesis resulted in decreased purine nucleotide levels and enhanced 5-phosphoribosyl-1-pyrophosphate (PRPP) levels, with concurrent increased pyrimidine nucleotide levels. The Me-tIMP concentration increased proportionally with the concentration of Me-MPR. High Me-tIMP concentration also caused inhibition of PRPP synthesis. Maximal accumulation of PRPP thus occurred at low Me-MPR concentrations. As little as 0.2 μM Me-MPR resulted already after 2 h in maximal inhibition of formation of adenine and guanine nucleotides, caused by inhibition of purine de novo synthesis by Me-tIMP. Under these circumstances increased intracellular PRPP concentrations could be demonstrated, resulting in increased levels of pyrimidine nucleotides. So, in Molt F4 cells, formation of Me-tIMP form Me-MPR results in cytotoxicity by inhibition of purine de novo synthesis. 相似文献
4.
Abstract: Different neurotransmitter receptor agonists [carbachol, serotonin, noradrenaline, histamine, endothelin-1, and trans -(1 S ,3 R )-aminocyclopentyl-1,3-dicarboxylic acid ( trans -ACPD)], known as stimuli of phospholipase C in brain tissue, were tested for phospholipase D stimulation in [32 P]Pi -prelabeled rat brain cortical and hippocampal slices. The accumulation of [32 P]phosphatidylethanol was measured as an index of phospholipase D-catalyzed transphosphatidylation in the presence of ethanol. Among the six neurotransmitter receptor agonists tested, only noradrenaline, histamine, endothelin-1, and trans -ACPD stimulated phospholipase D in hippocampus and cortex, an effect that was strictly dependent of the presence of millimolar extracellular calcium concentrations. The effect of histamine (EC50 18 µ M ) was inhibited by the H1 receptor antagonist mepyramine with a K i constant of 0.7 n M and was resistant to H2 and H3 receptor antagonists (ranitidine and tioperamide, respectively). Endothelin-1-stimulated phospholipase D (EC50 44 n M ) was not blocked by BQ-123, a specific antagonist of the ETA receptor. Endothelin-3 and the specific ETB receptor agonist safarotoxin 6c were also able to stimulate phospholipase D with efficacies similar to that of endothelin-1, and EC50 values of 16 and 3 n M , respectively. These results show that histamine and endothelin-1 stimulate phospholipase D in rat brain through H1 and ETB receptors, respectively. 相似文献
5.
Elisabet Font Mercedes Sitges Fausto G. Hegardt 《Biochemical and biophysical research communications》1982,105(2):705-710
Rat liver homogeneous 32P-labeled hydroxy methylglutaryl coenzyme A reductase, was treated independently with CNBr and trypsin and the resulting [32P]phosphopeptides were analyzed by disc gel electrophoresis. CNBr treatment produced only one 32P-fragment of Mr 18,000. The time course of trypsin hydrolysis initially showed the appearance of some phosphopeptides, which were lately converted in two phosphopeptides of low Mr. These results provide direct support for the concept that hydroxy methyl glutaryl coenzyme A reductase kinase solubilized from microsomes phosphorylates only two sites or set of sites in the reductase molecule. 相似文献
6.
Previous autoradiographic studies aimed at showing neurones using GABA as their neurotransmitter have been hampered by the fact that the substance is a ubiquitous metabolite and therefore accumulated by a large variety of cells, including glia. Consequently, GABA uptake markers without this widespread uptake are desirable, and one, [3H]isoguvacine, has shown promising results in autoradiographic experiments. Its uptake has now been further studied with quantitative radiochemical techniques.
The uptake of the drug was slow compared to GABA uptake and reached a tissue/medium ratio of about 3 after 120 min. The uptake could be inhibited by GABA, beta-alanine or ouabain, and by incubating the retinas at 0°C. The uptake kinetics were complex but suggested a high affinity uptake system (Km about 10−8 M) and perhaps one or several systems with lower affinities.
The results indicate that [3H]isoguvacine and [3H]GABA are accumulated and retained by the same neurones, which most likely use GABA as their neurotransmitter. 相似文献
7.
To determine the origin and the circulation of waters in the different areas of the Ebrié lagoon (Ivory Coast), ionic concentrations (K+ Cl-) and isotopic (18O) measurements were performed. Sixty stations were sampled. Chemical and isotopic analyses were made thrice during a hydrological cycle: in May 1986, at the end of the great dry season; in October 1986, during the maximum of rainfall, in December 1987, after the Comoe river peak flow. From a hydrodynamical point of view, the results reported in this work indicate that the lagoon comprises four distinctive areas. The first is filled with freshwater all the year round and is characterized by an weak isotopic enrichment (these waters are of continental origin and annually renewed); the second corresponds to oligohaline waters highly enriched in18O (waters essentially of continental origin and poorly renewed); the third area is constituted of a mixture of waters of continental and oceanic origins. The latter group can be separated into two subgroups: a group completely renewed by oceanic water during the dry season and another group totally renewed by freshwater during the rainy and flood seasons. 相似文献
8.
In general, the rate of nitrogen fixation decreased when the lichen Peltigera canina (L.) Willd. was exposed to sulfur dioxide gas at levels from 0.1 to 500 ppm; at 30 ppm, however, nitrogen fixation was stimulated. Chlorophyll content decreased as level of sulfur dioxide increased. 相似文献
9.
10.
Elisabet Barbero-Camps Vicente Roca-Agujetas Isabel Bartolessis Cristina de Dios Jose C. Fernández-Checa Montserrat Marí 《Autophagy》2018,14(7):1129-1154
Macroautophagy/autophagy failure with the accumulation of autophagosomes is an early neuropathological feature of Alzheimer disease (AD) that directly affects amyloid beta (Aβ) metabolism. Although loss of presenilin 1 function has been reported to impair lysosomal function and prevent autophagy flux, the detailed mechanism leading to autophagy dysfunction in AD remains to be elucidated. The resemblance between pathological hallmarks of AD and Niemann-Pick Type C disease, including endosome-lysosome abnormalities and impaired autophagy, suggests cholesterol accumulation as a common link. Using a mouse model of AD (APP-PSEN1-SREBF2 mice), expressing chimeric mouse-human amyloid precursor protein with the familial Alzheimer Swedish mutation (APP695swe) and mutant presenilin 1 (PSEN1-dE9), together with a dominant-positive, truncated and active form of SREBF2/SREBP2 (sterol regulatory element binding factor 2), we demonstrated that high brain cholesterol enhanced autophagosome formation, but disrupted its fusion with endosomal-lysosomal vesicles. The combination of these alterations resulted in impaired degradation of Aβ and endogenous MAPT (microtubule associated protein tau), and stimulated autophagy-dependent Aβ secretion. Exacerbated Aβ-induced oxidative stress in APP-PSEN1-SREBF2 mice, due to cholesterol-mediated depletion of mitochondrial glutathione/mGSH, is critical for autophagy induction. In agreement, in vivo mitochondrial GSH recovery with GSH ethyl ester, inhibited autophagosome synthesis by preventing the oxidative inhibition of ATG4B deconjugation activity exerted by Aβ. Moreover, cholesterol-enrichment within the endosomes-lysosomes modified the levels and membrane distribution of RAB7A and SNAP receptors (SNAREs), which affected its fusogenic ability. Accordingly, in vivo treatment with 2-hydroxypropyl-β-cyclodextrin completely rescued these alterations, making it a potential therapeutic tool for AD. 相似文献