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排序方式: 共有86条查询结果,搜索用时 15 毫秒
1.
Hanna Zirath Anna Frenzel Ganna Oliynyk Lova Segerstr?m Ulrica K. Westermark Karin Larsson Matilda Munksgaard Persson Kjell Hultenby Janne Lehti? Christer Einvik Sven P?hlman Per Kogner Per-Johan Jakobsson Marie Arsenian Henriksson 《Proceedings of the National Academy of Sciences of the United States of America》2013,110(25):10258-10263
The MYC genes are the most frequently activated oncogenes in human tumors and are hence attractive therapeutic targets. MYCN amplification leads to poor clinical outcome in childhood neuroblastoma, yet strategies to modulate the function of MYCN do not exist. Here we show that 10058-F4, a characterized c-MYC/Max inhibitor, also targets the MYCN/Max interaction, leading to cell cycle arrest, apoptosis, and neuronal differentiation in MYCN-amplified neuroblastoma cells and to increased survival of MYCN transgenic mice. We also report the discovery that inhibition of MYC is accompanied by accumulation of intracellular lipid droplets in tumor cells as a direct consequence of mitochondrial dysfunction. This study expands on the current knowledge of how MYC proteins control the metabolic reprogramming of cancer cells, especially highlighting lipid metabolism and the respiratory chain as important pathways involved in neuroblastoma pathogenesis. Together our data support direct MYC inhibition as a promising strategy for the treatment of MYC-driven tumors. 相似文献
2.
Pogoryelov D Klyszejko AL Krasnoselska GO Heller EM Leone V Langer JD Vonck J Müller DJ Faraldo-Gómez JD Meier T 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(25):E1599-E1608
ATP synthase membrane rotors consist of a ring of c-subunits whose stoichiometry is constant for a given species but variable across different ones. We investigated the importance of c/c-subunit contacts by site-directed mutagenesis of a conserved stretch of glycines (GxGxGxGxG) in a bacterial c(11) ring. Structural and biochemical studies show a direct, specific influence on the c-subunit stoichiometry, revealing c(<11), c(12), c(13), c(14), and c(>14) rings. Molecular dynamics simulations rationalize this effect in terms of the energetics and geometry of the c-subunit interfaces. Quantitative data from a spectroscopic interaction study demonstrate that the complex assembly is independent of the c-ring size. Real-time ATP synthesis experiments in proteoliposomes show the mutant enzyme, harboring the larger c(12) instead of c(11), is functional at lower ion motive force. The high degree of compliance in the architecture of the ATP synthase rotor offers a rationale for the natural diversity of c-ring stoichiometries, which likely reflect adaptations to specific bioenergetic demands. These results provide the basis for bioengineering ATP synthases with customized ion-to-ATP ratios, by sequence modifications. 相似文献
3.
Panasyuk G Nemazanyy I Ovcharenko G Lyzogubov V Gout I Filonenko V 《Hybridoma (2005)》2005,24(4):206-210
Protein kinase 2 (CK2) is a ubiquitous and constitutively active serine/threonine protein kinase with various cell functions. It typically forms tetrameric complexes consisting of two catalytic (alpha and/or (alpha') and two regulatory (beta) subunits. The aim of this study was to produce monoclonal antibodies (MAbs) against the CK2beta subunit and to characterize their suitability for Western blotting, immunoprecipitation, and immunohistochemical applications. Bacterially expressed CK2beta-6His-GST recombinant protein has been used as an antigen. Balb/c mice were immunized and given a final boost, and their spleen cells were collected and fused with SP2/0 myeloma cells using PEG 2000. The fused cells were then selected in the HAT-RPMI medium. Anti- CK2beta high-titer antibody-producing hybridoma cell lines were identified by enzyme-linked immunosorbent assay (ELISA) and then subcloned by limiting dilution in HT-RPMI medium supplemented with 20% fetal bovine serum (FBS). A total of 10 IgG-producing cell lines were selected and further tested for their reactivity with the CK2beta subunit using ELISA, Western blots, immunoprecipitation, and immunostaining of formaldehyde-fixed paraffin-embedded tissue sections. The results obtained clearly indicate that several clones produce antibodies that recognize specifically recombinant and endogenous CK2beta subunit in Western blotting and immunoprecipitation, and are suitable for immunohistochemical analysis. In summary, the produced antibodies will be useful for researchers investigating signaling pathways involving CK2 kinase and their deregulation in human pathologies. 相似文献
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Karabatsou K O'Kelly C Ganna A Dehdashti AR Gentili F 《British journal of neurosurgery》2008,22(5):630-635
The endoscopic technique is increasingly being used for the resection of pituitary adenomas. Its efficacy and safety have been generally accepted, but its impact on the quality of life of the patients treated has not been previously addressed. Most of the studies assessing the quality of life after long-term cure of pituitary adenomas suggest a significantly impaired quality of life (QoL) in all subgroups of pituitary tumours. In our study we analyse QoL data following endoscopic surgery, and attempt comparisons with normative and data from standard approaches. The validated health questionnaire SF-36 was sent to 80 patients who had undergone pure endoscopic resection of a pituitary adenoma. Fifty-four patients returned the completed questionnaire. Outcomes were compared with normative data for the Short Form-36 (SF-36) Heath survey for the general Canadian population. We also compared the results amongst different types of adenomas. We attempted a comparison to previous studies on quality of life for patients who underwent conventional trans-sphenoidal surgery. Our study suggests only minimal impairment of quality of life in patients after successful treatment of pituitary adenomas using the endoscopic approach. There were only very few differences in the perceived quality of life within the different subgroups of adenomas. There was a trend to improved scores in the endoscopic group compared with previous studies in patients treated by conventional approaches. Whilst our data suggest minimal impact on the quality of life for patients after endoscopic removal of pituitary adenomas, further studies with larger number of patients and longer follow-up are required to encourage this finding. 相似文献
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Ganna Balagura Giulia Iapadre Alberto Verrotti 《Expert opinion on pharmacotherapy》2013,14(12):1449-1456
ABSTRACTIntroduction: Sodium valproate is a widely used anti-epileptic drug with a broad spectrum of activity and mechanism of action. It has consequently been the first-line drug for most seizure types in children for the past fifty years. A wide range of side effects come along with these exceptional properties, including teratogenicity and neuro-cognitive impairments in offspring. Therefore, epilepsy treatment in children and adolescents should be reassessed in light of newer antiepileptic drugs as well as a more targeted-approach with older drugs.Areas covered: The authors review the main concerns of valproate use in terms of adverse effects on different systems and drug interactions. The current alternatives to valproate in absence, myoclonic, tonic-clonic and focal onset seizures in children/adolescents are also reviewed.Expert opinion: There are several issues that research should address in antiepileptic therapy and in clinical studies with children, given the peculiarity of this population. Future perspectives in epilepsy therapy should now lead towards an individualized treatment. 相似文献
9.
Deng X Xiong X Khomenko T Sandor Z Osapay K Tolstanova G Shiloach J Chen L Folkman J Szabo S 《Digestive diseases and sciences》2011,56(10):2792-2801
Background
Despite recent advances and better understanding of the etiology and the pathogenesis of gastrointestinal ulcer diseases, e.g., duodenal ulcer, the molecular events leading to ulcer development, delayed healing, and recurrence remain poorly elucidated. 相似文献10.
Herbert Schulz Ann‐Kathrin Ruppert Federico Zara Francesca Madia Michele Iacomino Maria S. Vari Ganna Balagura Carlo Minetti Pasquale Striano Amedeo Bianchi Carla Marini Renzo Guerrini Yvonne G. Weber Felicitas Becker Holger Lerche Claudia Kapser Christoph J. Schankin Wolfram S. Kunz Rikke S. Mller Karen L. Oliver Susannah T. Bellows Saul A. Mullen Samuel F. Berkovic Ingrid E. Scheffer Hande Caglayan Ugur Ozbek Per Hoffmann Sara Schramm Despina Tsortouktzidis Albert J. Becker Thomas Sander 《Epilepsia》2019,60(5):e31-e36
Juvenile myoclonic epilepsy (JME) is a common syndrome of genetic generalized epilepsies (GGEs). Linkage and association studies suggest that the gene encoding the bromodomain‐containing protein 2 (BRD2) may increase risk of JME. The present methylation and association study followed up a recent report highlighting that the BRD2 promoter CpG island (CpG76) is differentially hypermethylated in lymphoblastoid cells from Caucasian patients with JME compared to patients with other GGE subtypes and unaffected relatives. In contrast, we found a uniform low average percentage of methylation (<4.5%) for 13 CpG76‐CpGs in whole blood cells from 782 unrelated European Caucasians, including 116 JME patients, 196 patients with genetic absence epilepsies, and 470 control subjects. We also failed to confirm an allelic association of the BRD2 promoter single nucleotide polymorphism (SNP) rs3918149 with JME (Armitage trend test, P = 0.98), and we did not detect a substantial impact of SNP rs3918149 on CpG76 methylation in either 116 JME patients (methylation quantitative trait loci [meQTL], P = 0.29) or 470 German control subjects (meQTL, P = 0.55). Our results do not support the previous observation that a high DNA methylation level of the BRD2 promoter CpG76 island is a prevalent epigenetic motif associated with JME in Caucasians. 相似文献