全文获取类型
收费全文 | 80739篇 |
免费 | 4562篇 |
国内免费 | 9篇 |
出版年
2023年 | 458篇 |
2021年 | 934篇 |
2020年 | 846篇 |
2019年 | 817篇 |
2018年 | 2190篇 |
2017年 | 1926篇 |
2016年 | 2608篇 |
2015年 | 3445篇 |
2014年 | 3526篇 |
2013年 | 4652篇 |
2012年 | 5459篇 |
2011年 | 4769篇 |
2010年 | 3112篇 |
2009年 | 2297篇 |
2008年 | 3833篇 |
2007年 | 3612篇 |
2006年 | 3583篇 |
2005年 | 2996篇 |
2004年 | 3010篇 |
2003年 | 2679篇 |
2002年 | 2452篇 |
2001年 | 2019篇 |
2000年 | 1889篇 |
1999年 | 1448篇 |
1998年 | 631篇 |
1996年 | 505篇 |
1992年 | 906篇 |
1991年 | 831篇 |
1990年 | 815篇 |
1989年 | 888篇 |
1988年 | 728篇 |
1987年 | 749篇 |
1986年 | 685篇 |
1985年 | 749篇 |
1984年 | 620篇 |
1983年 | 543篇 |
1982年 | 453篇 |
1979年 | 668篇 |
1978年 | 488篇 |
1977年 | 488篇 |
1975年 | 584篇 |
1974年 | 623篇 |
1973年 | 595篇 |
1972年 | 547篇 |
1971年 | 491篇 |
1970年 | 536篇 |
1969年 | 610篇 |
1968年 | 573篇 |
1967年 | 479篇 |
1966年 | 466篇 |
排序方式: 共有10000条查询结果,搜索用时 67 毫秒
91.
This minireview is concerned with a re-examination of the locus of action and the possible peripheral mechanisms involved in the gastrointestinal (GI) stimulant effects of metoclopramide. Such a re-evaluation is opportune given the increasing use of this drug in the therapy of certain GI tract disorders. To provide an orientation on this subject the location in the GI tract and function of several relevant receptor types have been reviewed. In the past metoclopramide has been reported to enhance contractions of a variety of GI preparations to electrical stimulation, acetylcholine, carbachol and ganglion stimulants, to inhibit responses to alpha 2-adrenoreceptor agonists and 5-hydroxytryptamine, as well as blocking those to dopamine. Also in such preparations metoclopramide facilitates the release of acetylcholine to transmural stimulation. One important question is whether this effect is mediated via a specific prejunctional receptor. In this respect 2 suggestions have been made. Firstly that the drug may act as a preferential, prejunctional muscarinic antagonist thus inhibiting the negative feedback inhibition of acetylcholine release and secondly that metoclopramide may be a prejunctional agonist (partial) at 5-hydroxy-tryptamine receptors. Although the latter possibility appears most tenable at present, the involvement of a specific receptor remains to be confirmed. The important finding that dopamine receptors are probably not involved in the local stimulant effects of metoclopramide has important implications for future research orientated towards the discovery of a new generation of GI drugs lacking the side effects associated with central dopamine receptor blockade. Several compounds (cinitapride, BRL 20627A and cisapride) are now in the early stages of clinical evaluation. 相似文献
92.
Glycine transporter from rat brain stem and spinal cord is inactivated by specific sulfhydryl reagents. Modification of lysine residues also promotes a decrease of the transporter activity but in a lesser extent than that promoted by thiol group reagents. Mercurials showed a more marked inhibitory effect than maleimide derivatives. SH groups display a similar reactivity for p-chloromercuribenzenesulfonate (pCMBS) and mersalyl in synaptosomal membrane vesicles and proteoliposomes reconstituted with the solubilized transporter. However, different reactivity is observed with N-ethylmaleimide (MalNEt), the greatest effect being attained in membrane vesicles. The rate of inactivation by pCMBS and MalNEt is pseudo-first-order showing time- and concentration-dependence. pCMBS and MalNEt decrease the Vmax for glycine transport and to a lesser extent act on the apparent Km. Treatment with dithiothreitol (DTT) of the transporter modified by pCMBS results in a complete restoration of transporter activity indicating that the effect exercised by the reagent is specific for cysteine residues on the protein. It is concluded that SH groups are involved in the glycine transporter function and that these critical residues are mostly located in a relatively hydrophilic environment of the protein. 相似文献
93.
94.
95.
Restriction mapping of the rRNA genes from Artemia larvae 总被引:4,自引:0,他引:4
J Cruces J Sebastián J Renart 《Biochemical and biophysical research communications》1981,98(2):404-409
A restriction endonuclease analysis of the genes coding for the ribosomal RNA from Artemia larvae has shown that these genes consist of a repeat unit of 16.2 kilobase pairs (10.7 Mdaltons) and that the repeat unit seems to be homogeneous in size. 相似文献
96.
T Abe S Alemá R Miledi 《Proceedings of the Royal Society of London. Series B, Containing papers of a Biological character. Royal Society (Great Britain)》1980,207(1169):487-490
It has recently been claimed that our beta-bungarotoxin preparation contained three contaminants, including a postsynaptic toxin. We have extended our purification procedure and found no evidence of such contaminants. 相似文献
97.
98.
99.
David Dávila Silvia Fernández Ignacio Torres-Alemán 《The Journal of biological chemistry》2016,291(5):2510-2523
Disruption of insulin-like growth factor I (IGF-I) signaling is a key step in the development of cancer or neurodegeneration. For example, interference of the prosurvival IGF-I/AKT/FOXO3 pathway by redox activation of the stress kinases p38 and JNK is instrumental in neuronal death by oxidative stress. However, in astrocytes, IGF-I retains its protective action against oxidative stress. The molecular mechanisms underlying this cell-specific protection remain obscure but may be relevant to unveil new ways to combat IGF-I/insulin resistance. Here, we describe that, in astrocytes exposed to oxidative stress by hydrogen peroxide (H2O2), p38 activation did not inhibit AKT (protein kinase B) activation by IGF-I, which is in contrast to our previous observations in neurons. Rather, stimulation of AKT by IGF-I was significantly higher and more sustained in astrocytes than in neurons either under normal or oxidative conditions. This may be explained by phosphorylation of the phosphatase PTEN at the plasma membrane in response to IGF-I, inducing its cytosolic translocation and preserving in this way AKT activity. Stimulation of AKT by IGF-I, mimicked also by a constitutively active AKT mutant, reduced oxidative stress levels and cell death in H2O2-exposed astrocytes, boosting their neuroprotective action in co-cultured neurons. These results indicate that armoring of AKT activation by IGF-I is crucial to preserve its cytoprotective effect in astrocytes and may form part of the brain defense mechanism against oxidative stress injury. 相似文献
100.
F. Šrámek 《Biologia Plantarum》1999,42(4):582-582