全文获取类型
收费全文 | 389篇 |
免费 | 40篇 |
出版年
2022年 | 4篇 |
2021年 | 7篇 |
2019年 | 4篇 |
2018年 | 6篇 |
2017年 | 3篇 |
2016年 | 12篇 |
2015年 | 17篇 |
2014年 | 23篇 |
2013年 | 21篇 |
2012年 | 21篇 |
2011年 | 35篇 |
2010年 | 14篇 |
2009年 | 10篇 |
2008年 | 19篇 |
2007年 | 22篇 |
2006年 | 12篇 |
2005年 | 17篇 |
2004年 | 10篇 |
2003年 | 9篇 |
2002年 | 9篇 |
2001年 | 9篇 |
2000年 | 17篇 |
1999年 | 16篇 |
1998年 | 7篇 |
1997年 | 5篇 |
1996年 | 7篇 |
1995年 | 4篇 |
1994年 | 4篇 |
1993年 | 2篇 |
1992年 | 6篇 |
1991年 | 5篇 |
1990年 | 4篇 |
1989年 | 4篇 |
1988年 | 10篇 |
1987年 | 4篇 |
1986年 | 5篇 |
1985年 | 4篇 |
1984年 | 4篇 |
1982年 | 2篇 |
1981年 | 2篇 |
1980年 | 5篇 |
1977年 | 5篇 |
1976年 | 2篇 |
1975年 | 1篇 |
1974年 | 5篇 |
1973年 | 5篇 |
1972年 | 1篇 |
1971年 | 2篇 |
1970年 | 3篇 |
1967年 | 1篇 |
排序方式: 共有429条查询结果,搜索用时 31 毫秒
411.
412.
P Duquesnoy M L Sobrier B Duriez F Dastot C R Buchanan M O Savage M A Preece C T Craescu Y Blouquit M Goossens et al. 《The EMBO journal》1994,13(6):1386-1395
Growth hormone (GH) elicits a variety of biological activities mainly mediated by the GH receptor (GHR), a transmembrane protein that, based on in vitro studies, seemed to function as a homodimer. To test this hypothesis directly, we investigated patients displaying the classic features of Laron syndrome (familial GH resistance characterized by severe dwarfism and metabolic dysfunction), except for the presence of normal binding activity of the plasma GH-binding protein, a molecule that derives from the exoplasmic-coding domain of the GHR gene. In two unrelated families, the same GHR mutation was identified, resulting in the substitution of a highly conserved aspartate residue by histidine at position 152 (D152H) of the exoplasmic domain, within the postulated interface sequence involved in homodimerization. The recombinant mutated receptor protein was correctly expressed at the plasma membrane. It displayed subnormal GH-binding activity, a finding in agreement with the X-ray crystal structure data inferring this aspartate residue outside the GH-binding domain. However, mAb-based studies suggested the critical role of aspartate 152 in the proper folding of the interface area. We show that a recombinant soluble form of the mutant receptor is unable to dimerize, the D152H substitution also preventing the formation of heterodimers of wild-type and mutant molecules. These results provide in vivo evidence that monomeric receptors are inactive and that receptor dimerization is involved in the primary signalling of the GH-associated growth-promoting and metabolic actions. 相似文献
413.
Background
Despite its clinical importance, a dearth of information exists on the cellular and molecular mechanisms that underpin brain stem death. A suitable neural substrate for mechanistic delineation on brain stem death resides in the rostral ventrolateral medulla (RVLM) because it is the origin of a life-and-death signal that sequentially increases (pro-life) and decreases (pro-death) to reflect the advancing central cardiovascular regulatory dysfunction during the progression towards brain stem death in critically ill patients. The present study evaluated the hypothesis that heme oxygnase-1 (HO-1) may play a pro-life role as an interposing signal between hypoxia-inducible factor-1 (HIF-1) and nitric oxide synthase I (NOS I)/protein kinase G (PKG) cascade in RVLM, which sustains central cardiovascular regulatory functions during brain stem death. 相似文献414.
415.
Summary With the use of the unlabeled antibody peroxidase-antiperoxidase (PAP) technique at the light microscopic level, it was shown that the preoptico-hypophysial neurosecretory system of the adult migrating Lampetra fluviatilis is a vasotocinergic system. It does not synthesize vasopressin. The results are entirely consistent with earlier chromatographic and pharmacological indications that it produces little or no oxytocin-like peptide hormone. In the adenohypophysis, immunoreactive neurohypophysial peptidergic fibres are absent.This investigation was supported by a grant from the Belgian Nationaal Fonds voor Geneeskundig Wetenschappelijk Onderzoek 相似文献
416.
Tiphaine Rogez-Florent Laurence Goossens Anne-Sophie Drucbert Sophie Duban-Deweer Perrine Six Patrick Depreux Pierre-Marie Danzé Jean-François Goossens Catherine Foulon 《Analytical biochemistry》2016
This work was dedicated to the development of a reliable SPR method allowing the simultaneous and quick determination of the affinity and selectivity of designed sulfonamide derivatives for hCAIX and hCAXII versus hCAII, in order to provide an efficient tool to discover drugs for anticancer therapy of solid tumors. We performed for the first time a comparison of two immobilization approaches of hCA isoforms. First one relies on the use of an amine coupling strategy, using a CM7 chip to obtain higher immobilization levels than with a CM5 chip and consequently the affinity with an higher precision (CV% < 10%). The second corresponds to a capture of proteins on a streptavidin chip, named CAP chip, after optimization of biotinylation conditions (amine versus carboxyl coupling, biotin to protein ratio). Thanks to the amine coupling approach, only hCAII and hCAXII isoforms were efficiently biotinylated to reach relevant immobilization (3000 RU and 2700 RU, respectively) to perform affinity studies. For hCAIX, despite a successful biotinylation, capture on the CAP chip was a failure. Finally, concordance between affinities obtained for the three derivatives to CAs isozymes on both chips has allowed to valid the approaches for a further screening of new derivatives. 相似文献
417.
M Bonduelle W Lissens A Goossens L De Catte W Foulon R Denis E Jauniaux I Liebaers 《Genetic counseling (Geneva, Switzerland)》1991,2(4):227-232
Two cases of beta-glucuronidase deficiency (mucopolysaccharidosis VII), presented with fetal hydrops at 20 and 26 weeks of gestation. The enzyme deficiency was observed in cultured amniotic fluid cells and in fetal plasma from cord-blood and was confirmed after termination of pregnancy. A third case presented with transient ascites at 6.5 months of gestation. Mild dysmorphic features at birth and gradual neurological deterioration were observed. Deficiency of beta-galactosidase was documented confirming a GM1 gangliosidosis. Evidence has accumulated that fetuses affected by lysosomal diseases, may present with transient or persistent hydrops fetalis. The exact frequency is however not known. Further diagnostic studies in persistent or transient hydrops fetalis, looking for lysosomal and other metabolic diseases, whenever major causes of hydrops fetalis have been excluded, are therefore indicated. Amniocentesis and cordocentesis should always be performed. 相似文献
418.
Luis J V Galietta Patrick Pagesy Chiara Folli Emanuela Caci Leila Romio Bruno Costes Elena Nicolis Giulio Cabrini Michel Goossens Roberto Ravazzolo Olga Zegarra-Moran 《Journal of immunology (Baltimore, Md. : 1950)》2002,168(2):839-845
Recent data show that proinflammatory stimuli may modify significantly ion transport in the airway epithelium and therefore the properties of the airway surface fluid. We have studied the effect of IL-4, a cytokine involved in the pathogenesis of asthma, on transepithelial ion transport in the human bronchial epithelium in vitro. Incubation of polarized bronchial epithelial cells with IL-4 for 6-48 h causes a marked inhibition of the amiloride-sensitive Na(+) channel as measured in short circuit current experiments. On the other hand, IL-4 evokes a 2-fold increase in the current activated by a cAMP analog, which reflects the activity of the cystic fibrosis transmembrane conductance regulator (CFTR). Similarly, IL-4 enhances the response to apical UTP, an agonist that activates Ca(2+)-dependent Cl(-) channels. These effects are mimicked by IL-13 and blocked by an antagonist of IL-4Ralpha. RT-PCR experiments show that IL-4 elicits a 7-fold decrease in the level of the gamma amiloride-sensitive Na(+) channel mRNA, one of the subunits of the amiloride-sensitive Na(+) channel, and an increase in CFTR mRNA. Our data suggest that IL-4 may favor the hydration of the airway surface by decreasing Na(+) absorption and increasing Cl(-) secretion. This could be required to fluidify the mucus, which is hypersecreted during inflammatory conditions. On the other hand, the modifications of ion transport could also affect the ion composition of airway surface fluid. 相似文献
419.
420.
Abstract By means of a newly developed medium, cholera-like enterotoxin production by Campylobacter jejuni could be shown in 25 C. jejuni strains isolated from diarrheic cases. This new medium was found to yield a higher amount of enterotoxin than the two previously reported media for this purpose. Neutralization of the activity of the toxin to cause morphological changes of Chinese hamster ovary (CHO) cells by antisera against cholera toxin and heat-labile enterotoxins of Escherichia coli (LTh and LTp ) was also demonstrated, indicating a close immunological relation of these toxins. 相似文献