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111.
112.
Gastric cancers emerging after H. pylori eradication arise exclusively from non-acid-secreting areas
Iijima K Abe Y Koike T Uno K Endo H Hatta W Asano N Asanuma K Imatani A Shimosegawa T 《The Tohoku journal of experimental medicine》2012,226(1):45-53
Although Helicobacter pylori (H. pylori) eradication has some inhibitory effects on the subsequent development of gastric cancer, there are sporadic cases of gastric cancer even after successful eradication. The pathogenesis of gastric cancer emerging after H. pylori eradication remains to be clarified. In this study, employing Congo-red chromoendoscopy, which is capable of visualizing the acid-secreting fundic mucosa, we investigated the topographic relationship of the acid secretion pattern to the occurrence site of gastric cancers emerging after eradication. Fourteen consecutive patients who suffered from new gastric cancer after eradication, defined as lesions that were discovered at least 2 years after the eradication, were prospectively enrolled. Whether the neoplasias arose from acid-secreting or non-acid-secreting areas was evaluated with Congo-red chromoendoscopy. Biopsy specimens taken from the two areas were subjected to histologic evaluation and immunohistochemistry for Ki-67 and p53. The mean period from the eradication to the subsequent occurrence of gastric cancer was 74 (44) months. There were two cancer lesions in 5 cases, and thus there was a total 19 lesions from 14 cases. Congo-red chromoendoscopy revealed that all 19 lesions arose exclusively from non-acid-secreting areas. Histological examination revealed sustained hyperproliferation and accumulation of p53 protein was frequently detectable in non-acid-secreting areas. Genetic alteration such as p53 mutation seems to be already present in the residual non-acid-secreting areas after eradication, areas that could be the origin of gastric carcinogenesis after eradication. Identification of such high-risk areas should be a promising approach for estimating the individual cancer risk after eradication. 相似文献
113.
Sacherer M Sedej S Wakuła P Wallner M Vos M Kockskämper J Stiegler P Sereinigg M von Lewinski D Antoons G Pieske B Heinzel F;CONTICA investigators 《British journal of pharmacology》2012,167(3):493-504
BACKGROUND AND PURPOSE
Ca2+ leak from the sarcoplasmic reticulum (SR) via ryanodine receptors (RyR2s) contributes to cardiomyocyte dysfunction. RyR2 Ca2+ leak has been related to RyR2 phosphorylation. In these conditions, JTV519 (K201), a 1,4-benzothiazepine derivative and multi-channel blocker, stabilizes RyR2s and decrease SR Ca2+ leak. We investigated whether JTV519 stabilizes RyR2s without increasing RyR2 phosphorylation in mice and in non-failing human myocardium and explored underlying mechanisms.EXPERIMENTAL APPROACH
SR Ca2+ leak was induced by ouabain in murine cardiomyocytes. [Ca2+]-transients, SR Ca2+ load and RyR2-mediated Ca2+ leak (sparks/waves) were quantified, with or without JTV519 (1 µmol·L−1). Contribution of Ca2+-/calmodulin-dependent kinase II (CaMKII) was assessed by KN-93 and Western blot (RyR2-Ser2814 phosphorylation). Effects of JTV519 on contractile force were investigated in non-failing human ventricular trabeculae.KEY RESULTS
Ouabain increased systolic and diastolic cytosolic [Ca2+]i, SR [Ca2+], and SR Ca2+ leak (Ca2+ spark (SparkF) and Ca2+ wave frequency), independently of CaMKII and RyR-Ser2814 phosphorylation. JTV519 decreased SparkF but also SR Ca2+ load. At matched SR [Ca2+], Ca2+ leak was significantly reduced by JTV519, but it had no effect on fractional Ca2+ release or Ca2+ wave propagation velocity. In human muscle, JTV519 was negatively inotropic at baseline but significantly enhanced ouabain-induced force and reduced its deleterious effects on diastolic function.CONCLUSIONS AND IMPLICATIONS
JTV519 was effective in reducing SR Ca2+ leak by specifically regulating RyR2 opening at diastolic [Ca2+]i in the absence of increased RyR2 phosphorylation at Ser2814, extending the potential use of JTV519 to conditions of acute cellular Ca2+ overload. 相似文献114.
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Diane Waku‐Kouomou François Freymuth Isabelle Parent du Châtelet T. Fabian Wild Branka Horvat 《Journal of medical virology》2010,82(6):1033-1043
In 2008, measles reappeared in France in a series of outbreaks. During this period, 604 measles cases were reported to a routine surveillance system and 305 (50%) of these cases were then confirmed in the laboratory. To understand better the current epidemiological situation and the circulation of different measles strains, a phylogenetic characterization of 113 (19%) of the measles cases from these outbreaks was performed. All measles cases met the WHO clinical criteria and were confirmed either by laboratory detection of measles‐specific IgM and/or by detection of the virus genome by polymerase chain reaction (PCR) and viral isolation. PCR products generated from blood, oral fluid, urine, or nasopharyngeal‐swab samples were sequenced for molecular epidemiology studies. Phylogenetic analysis showed a co‐circulation of genotypes D4 and D5 during the first measles outbreak in the city of Reims in early 2008. Over the course of the year, the A, B3.2, D8, and D9 genotypes also appeared. The data from this study show the simultaneous circulation of several measles genotypes in France and describe genotypes D8 and D9 for the first time in this country. The data also suggest that there are still many pockets of unvaccinated individuals helping to maintain the circulation of measles virus in the population. Phylogenetic studies allowed the corroboration of epidemiologic links and showed that nosocomial transmission can create significant risk for measles dissemination. Finally, the pattern of changes in viral genotypes during 2008 suggests a regular introduction of measles strains from abroad. J. Med. Virol. 82:1033–1043, 2010. © 2010 Wiley‐Liss, Inc. 相似文献