全文获取类型
收费全文 | 1018篇 |
免费 | 76篇 |
出版年
2024年 | 1篇 |
2023年 | 4篇 |
2022年 | 8篇 |
2021年 | 19篇 |
2020年 | 12篇 |
2019年 | 18篇 |
2018年 | 20篇 |
2017年 | 22篇 |
2016年 | 23篇 |
2015年 | 59篇 |
2014年 | 46篇 |
2013年 | 97篇 |
2012年 | 110篇 |
2011年 | 86篇 |
2010年 | 67篇 |
2009年 | 41篇 |
2008年 | 60篇 |
2007年 | 66篇 |
2006年 | 60篇 |
2005年 | 64篇 |
2004年 | 62篇 |
2003年 | 48篇 |
2002年 | 27篇 |
2001年 | 5篇 |
2000年 | 6篇 |
1999年 | 5篇 |
1998年 | 7篇 |
1997年 | 5篇 |
1996年 | 7篇 |
1995年 | 4篇 |
1994年 | 4篇 |
1993年 | 7篇 |
1992年 | 6篇 |
1991年 | 1篇 |
1990年 | 2篇 |
1989年 | 1篇 |
1988年 | 2篇 |
1987年 | 1篇 |
1986年 | 3篇 |
1984年 | 1篇 |
1983年 | 1篇 |
1978年 | 3篇 |
1977年 | 1篇 |
1976年 | 1篇 |
1973年 | 1篇 |
排序方式: 共有1094条查询结果,搜索用时 15 毫秒
51.
McCarthy J Hopwood F Oxley D Laver M Castagna A Righetti PG Williams K Herbert B 《Journal of proteome research》2003,2(3):239-242
Carbamylation is widely quoted as being a problem in 2-D gel analysis and the associated sample preparation steps. This modification occurs when iso-cyanate, a urea break-down product, covalently modifies lysine residues, thus inducing a change in isoelectric point. Urea is used at up to 9 M concentrations in sample preparation and 2-D gels because of its ability to disrupt protein structure and effect denaturation without the need for ionic surfactants such as SDS. We have studied carbamylation using 7 M urea and 2 M thiourea, under a range of experimental temperatures to establish when, and if, it occurs and what can be done to minimize the modification. The actual time required for protein extraction from a tissue is usually short compared to the time required for procedures such as reduction and alkylation and IPG rehydration and focusing. Therefore, it is the temperature during these post-extraction procedures that is the most critical factor. Our experiments have shown that carbamylation does not occur during electrophoresis in the presence of urea, even with prolonged run-times. However, under poorly controlled sample preparation and storage conditions, it can become a major event. 相似文献
52.
Baratto MC Tattini M Galardi C Pinelli P Romani A Visioli F Basosi R Pogni R 《Free radical research》2003,37(4):405-412
The antioxidant properties of galloyl quinic derivatives isolated from Pistacia lentiscus L. leaves have been investigated by means of Electron Paramagnetic Resonance spectroscopy (EPR) and UV-Vis spectrophotometry. Antioxidant properties have been also estimated using the biologically relevant LDL test. The scavenger activities of gallic acid, 5- O -galloyl, 3,5- O -digalloyl, 3,4,5- O -trigalloyl quinic acid derivatives, have been estimated against 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, superoxide ( O 2 - ) radical, and hydroxyl (OH) radical. On the whole, the scavenger activity raised as the number of galloyl groups on the quinic acid skeleton increased. The half-inhibition concentrations (IC 50 ) of di- and tri-galloyl derivatives did not exceed 30 μM for all the tested free radicals. All the tested metabolites strongly reduced the oxidation of low-density lipoproteins (LDL), following a trend similar to that observed for the scavenger ability against OH radical. 相似文献
53.
54.
Onori L Aggio A Taddei G Loreto MF Ciccocioppo R Vicini R Tonini M 《American journal of physiology. Gastrointestinal and liver physiology》2003,285(2):G325-G331
In the gastrointestinal tract, tachykinin NK1 receptors are widely distributed in a number of neuronal and nonneuronal cells involved in the control of gut motor activity. In particular, in the rabbit isolated distal colon, which is a suitable model system to investigate the contribution of tachykinins as noncholinergic excitatory transmitters, the influence of NK1 receptors in the regulation of peristalsis is not known. The selective NK1-receptor antagonists SR-140333 (0.3 and 1 nM) and MEN-10930 (0.3-10 nM) significantly enhanced the velocity of rabbit colonic propulsion to submaximal stimulation. The prokinetic effect of SR-140333 was prevented by N(omega)-nitro-L-arginine (L-NNA), a nitric oxide synthase inhibitor, indicating that NK1 receptors located on nitrergic innervation exert a functional inhibitory restraint on the circular muscle and probably on descending excitatory and inhibitory pathways during propulsion. Conversely, the selective NK1-receptor agonist septide (3-10 nM) significantly inhibited colonic propulsion. In the presence of L-NNA, the inhibitory effect of septide was reverted into a prokinetic effect, which is probably mediated by the activation of postjunctional excitatory NK1 receptors. 相似文献
55.
Longo O Lamberti A Zambrano N Arcari P 《Bioscience, biotechnology, and biochemistry》2003,67(9):2048-2050
The stepwise chromatographic behaviour on DEAE-Sepharose of rat Fe65, a neuronal protein, was tested, using as eluants KCl, CaCl2, and MgCl2. Assays by western blot showed that Fe65 was eluted by CaCl2, at a ionic strength 20% lower than that of MgCl2 or KCl. Interestingly, in the case of a truncated Fe65, lacking a glutamic acid rich region at the N-terminus, the ionic strengths of the various eluants were almost identical. These results suggested a possible inhibitory role of calcium ions in the binding of the protein to DEAE and a specific affinity of these ions for long acidic stretches. 相似文献
56.
Esophageal cancer is generally characterised by relatively low incidence and mortality rates in Europe. However, a high-risk population for this tumour is resident in the north-east of Italy. Several studies have been conducted on this population of males confirming the major role of alcohol and tobacco consumption alone and in combination. The inhabitants of this area of Italy constitute an ideal target population for studies of molecular epidemiology aimed at elucidating the natural history of the disease which is still ill-defined, and the distribution of genetic alterations at a population level. 相似文献
57.
Bekman EP Saibo NJ Di Cataldo A Regalado AP Ricardo CP Rodrigues-Pousada C 《Planta》2000,211(5):663-672
1-Aminocyclopropane-1-carboxylate (ACC) synthase (ACS; EC 4.4.1.14) is the key regulatory enzyme of the ethylene biosynthetic
pathway and is encoded by a multigene family in Arabidopsis thaliana, tomato, mung bean and other plants. Southern blot analysis revealed the existence of at least five ACS genes in white lupin
(Lupinus albus L.) genome. Four complete and one partial sequences representing different ACS genes were cloned from the lupin genomic library.
The levels of expression of two of the genes, LA-ACS1 and LA-ACS3, were found to increase after hypocotyl wounding. Apparently, these two genes were up-regulated by exogenous IAA treatment
of seedlings. The LA-ACS3 mRNA levels were also elevated in the apical part of hypocotyl, which is reported to contain a high endogenous auxin concentration.
This gene may be involved in the auxin- and ethylene-controlled apical hook formation. The expression of the LA-ACS4 gene was found to be almost undetectable. This gene may represent a “silent” twin of LA-ACS5 as these two genes share a considerable level of homology in coding and non-coding regions. The LA-ACS5 mRNA is strongly up-regulated in the embryonic axis of germinating seeds at the time of radicle emergence, and was also found
in roots and hypocotyls of lupin seedlings.
Received: 19 July 1999 / Accepted: 3 March 2000 相似文献
58.
Annalisa Castagna Natascia Campostrini Federica Zaninotto Domenico Girelli 《Journal of Proteomics》2010,73(3):527-536
Hepcidin, a liver peptide hormone, is the central regulator of iron homeostasis. Hepcidin synthesis is modulated by iron stores, so that iron repletion increases its levels to prevent pathological overload, while iron deficiency strongly inhibits hepcidin to allow an increase in iron absorption from duodenal cells. The emerging pivotal role of hepcidin in iron homeostasis, along with its important links with basic pathways like inflammation, makes the availability of an accurate hepcidin assay as a potentially powerful investigative tool to improve our understanding as well as our diagnostic/prognostic capabilities in many human diseases. There has been a great interest worldwide in developing a reliable and widely applicable assay of the hormone in biological fluids. Being optimal for low-molecular-weight biomarkers, SELDI-TOF-MS has emerged as a valid tool for hepcidin assay. Here we review recent results obtained with this technique, as well as with other Mass Spectrometry-based and immunological methods. 相似文献
59.
60.
Marialuisa Moccia Qingsong Liu Teresa Guida Giorgia Federico Annalisa Brescia Zheng Zhao Hwan Geun Choi Xianming Deng Li Tan Jinhua Wang Marc Billaud Nathanael S. Gray Francesca Carlomagno Massimo Santoro 《PloS one》2015,10(6)
Oncogenic mutation of the RET receptor tyrosine kinase is observed in several human malignancies. Here, we describe three novel type II RET tyrosine kinase inhibitors (TKI), ALW-II-41-27, XMD15-44 and HG-6-63-01, that inhibit the cellular activity of oncogenic RET mutants at two digit nanomolar concentration. These three compounds shared a 3-trifluoromethyl-4-methylpiperazinephenyl pharmacophore that stabilizes the ‘DFG-out’ inactive conformation of RET activation loop. They blocked RET-mediated signaling and proliferation with an IC50 in the nM range in fibroblasts transformed by the RET/C634R and RET/M918T oncogenes. They also inhibited autophosphorylation of several additional oncogenic RET-derived point mutants and chimeric oncogenes. At a concentration of 10 nM, ALW-II-41-27, XMD15-44 and HG-6-63-01 inhibited RET kinase and signaling in human thyroid cancer cell lines carrying oncogenic RET alleles; they also inhibited proliferation of cancer, but not non-tumoral Nthy-ori-3-1, thyroid cells, with an IC50 in the nM range. The three compounds were capable of inhibiting the ‘gatekeeper’ V804M mutant which confers substantial resistance to established RET inhibitors. In conclusion, we have identified a type II TKI scaffold, shared by ALW-II-41-27, XMD15-44 and HG-6-63-01, that may be used as novel lead for the development of novel agents for the treatment of cancers harboring oncogenic activation of RET. 相似文献