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41.
Paolo Bergamo Ennio Cocca Rosanna Palumbo Marta Gogliettino Mose Rossi Gianna Palmieri 《PloS one》2013,8(11)
This study describes the investigation of the efficiency of conjugated linoleic acid (CLA) isomers in reducing cancer cells viability exploring the role of the oxidative stress and acylpeptide hydrolase (APEH)/proteasome mediated pathways on pro-apoptotic activity of the isomer trans10,cis12 (t10,c12)-CLA. The basal activity/expression levels of APEH and proteasome (β-5 subunit) were preliminarily measured in eight cancer cell lines and the functional relationship between these enzymes was clearly demonstrated through their strong positive correlation. t10,c12-CLA efficiently inhibited the activity of APEH and proteasome isoforms in cell-free assays and the negative correlation between cell viability and caspase 3 activity confirmed the pro-apoptotic role of this isomer. Finally, modulatory effects of t10,c12-CLA on cellular redox status (intracellular glutathione, mRNA levels of antioxidant/detoxifying enzymes activated through NF-E2-related factor 2, Nrf2, pathway) and on APEH/β-5 activity/expression levels, were investigated in A375 melanoma cells. Dose- and time-dependent variations of the considered parameters were established and the resulting pro-apoptotic effects were shown to be associated with an alteration of the redox status and a down-regulation of APEH/proteasome pathway. Therefore, our results support the idea that these events are involved in ROS-dependent apoptosis of t10,c12-CLA-treated A375 cells. The combined inhibition, triggered by t10,c12-CLA, via the modulation of APEH/proteasome and Nrf2 pathway for treating melanoma, is suggested as a subject for further in vivo studies. 相似文献
42.
Tobias Raisch Giuseppe Ciossani Ennio dAmico Verena Cmentowski Sara Carmignani Stefano Maffini Felipe Merino Sabine Wohlgemuth Ingrid R Vetter Stefan Raunser Andrea Musacchio 《The EMBO journal》2022,41(9)
In metazoans, a ≈1 megadalton (MDa) multiprotein complex comprising the dynein–dynactin adaptor Spindly and the ROD–Zwilch–ZW10 (RZZ) complex is the building block of a fibrous biopolymer, the kinetochore fibrous corona. The corona assembles on mitotic kinetochores to promote microtubule capture and spindle assembly checkpoint (SAC) signaling. We report here a high‐resolution cryo‐EM structure that captures the essential features of the RZZ complex, including a farnesyl‐binding site required for Spindly binding. Using a highly predictive in vitro assay, we demonstrate that the SAC kinase MPS1 is necessary and sufficient for corona assembly at supercritical concentrations of the RZZ–Spindly (RZZS) complex, and describe the molecular mechanism of phosphorylation‐dependent filament nucleation. We identify several structural requirements for RZZS polymerization in rings and sheets. Finally, we identify determinants of kinetochore localization and corona assembly of Spindly. Our results describe a framework for the long‐sought‐for molecular basis of corona assembly on metazoan kinetochores. 相似文献
43.
Dr. Caterina De Vinci Giancarlo Pizza Diego Cuzzocrea Domenico Menniti Ernesto Aiello Paolo Maver Giuseppe Corrado Piero Romagnoli Ennio Dragoni Giuseppe LoConte Umberto Riolo Massimo Masi Giuseppe Severini Vittorio Fornarola Dimitri Viza 《Biotherapy》1996,9(1-3):133-138
Results of conventional treatment of female non-bacterial recurrent cystitis (NBRC) are discouraging. Most patients show an
unexpected high incidence of vaginal candidiasis, while their cell mediated immunity to Herpes simplex viruses (HSV) and Candida
antigens seems impaired, and it is known that the persistence of mucocutaneous chronic candidiasis is mainly due to a selective
defect of CMI to Canadida antigens.
Twenty nine women suffering of NBRC, and in whom previous treatment with antibiotics and non-steroid anti-inflammatory drugs
was unsuccessful, underwent oral transfer factor (TF) therapy. TF specific to Canadida and/or to HSV was administered bi-weekly
for the first 2 weeks, and then once a week for the following 6 months. No side effects were observed during treatment. The
total observation period of our cohort was 24379 days with 353 episodes of cystitis recorded and a cumulative relapse index
(RI) of 43. The observation period during and after treatment was 13920 days with 108 relapses and a cumulative RI of 23 (P
< 0.0001). It, thus, seems that specific TF may be capable of controlling NBRC and alleviate the symptoms. 相似文献
44.
Paola Perucca Roberto Mocchi Isabella Guardamagna Elisabetta Bassi Sabrina Sommatis Tiziana Nardo Ennio Prosperi Lucia Anna Stivala Ornella Cazzalini 《Biochimica et Biophysica Acta (BBA)/Molecular Cell Research》2018,1865(6):898-907
In mammalian cells, Nucleotide Excision Repair (NER) plays a role in removing DNA damage induced by UV radiation. In Global Genome-NER subpathway, DDB2 protein forms a complex with DDB1 (UV-DDB), recognizing photolesions. During DNA repair, DDB2 interacts directly with PCNA through a conserved region in N-terminal tail and this interaction is important for DDB2 degradation. In this work, we sought to investigate the role of DDB2-PCNA association in DNA repair and cell proliferation after UV-induced DNA damage. To this end, stable clones expressing DDB2Wt and DDB2PCNA- were used. We have found that cells expressing a mutant DDB2 show inefficient photolesions removal, and a concomitant lack of binding to damaged DNA in vitro. Unexpected cellular behaviour after DNA damage, such as UV-resistance, increased cell growth and motility were found in DDB2PCNA- stable cell clones, in which the most significant defects in cell cycle checkpoint were observed, suggesting a role in the new cellular phenotype. Based on these findings, we propose that DDB2-PCNA interaction may contribute to a correct DNA damage response for maintaining genome integrity. 相似文献
45.
Abstract: Synaptosomes from rat cerebellum were used to investigate the involvement of different glutamate receptor subtypes in the control of the synthesis of nitric oxide (NO), measured as its breakdown product nitrite (NO2-). Synaptosomes incubated in the presence of NAD|PH and l -arginine produced measurable levels of NO2-, which were reduced by addition of Nω-nitro-l -arginine methyl ester, an inhibitor of nitric oxide synthase. The selective ionotropic glutamate receptor agonist N-methyl-d -aspartate (NMDA) induced a pronounced increase in NO2-formation, which was prevented by Nω-nitro-l -arginine methyl ester and by the specific NMDA receptor antagonist Dl -2-amino-5-phosphonovaleric acid (AP-5). The NMDA-induced increase in NO2-formation was blocked by chelation of extracellular Ca2+ with EGTA. Both l -glutamate and the selective agonist for the metabotropic glutamate receptors (β)-1-aminocyclopentane-trans-1,3-dicarboxylic acid raised NO2-production, which retumed to control levels after addition of Nω-nitro-l -arginine methyl ester. The selective glutamate ionotropic receptor agonist (R,S)-α-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid did not cause any change in NO2 formation. The stimulatory effect of l -glutamate was blocked by the metabotropic glutamate receptor antagonist Dl -2-amino-4-phosphonobutyric acid but was unaffected by the selective NMDA receptor blocker AP-5. Removal of extracellular Ca2+ by EGTA did not affect the action of l -glutamate; whereas W-7, an inhibitor of calmodulin, and dantrolene, a compound that blocks the mobilization of Ca2+ from intracellular stores, abolished the effect of l -glutamate on NO2-formation. It is suggested that stimulation of ionotropic NMDA receptors activates NO metabolism by causing an influx of Ca2+ from the extracellular space, whereas activation of metabotropic receptors by l -glutamate provokes a mobilization of Ca2+ from intracellular stores, which stimulates nitric oxide synthase activity by forning Ca2+/calmodulin complexes. 相似文献
46.
47.
Luca G Calafiore R Basta G Ricci M Calvitti M Neri L Nastruzzi C Becchetti E Capitani S Brunetti P Rossi C 《AAPS PharmSciTech》2001,2(3):48-54
The purpose of this study was to assess whether Sertoli's cells would improve functional performance of homologous pancreatic islets within microcapsules. Purified rat Sertoli's cells were co-enveloped with islets in microcapsules that had been fabricated with alginic acid and poly-L-ornithine. Confocal laser microscopy was used to determine any mitogenic effects of Sertoli's cells on islets beta-cells. Insulin secretion from islets, with or without Sertoli's cells, was examined, and grafts of Sertoli's cells with islets in microcapsules into diabetic mice were carried out. Co-incubation of Sertoli's cells with islets resulted in a significant increase in the islet beta-cell mitotic rate, which was coupled with significantly higher insulin release under glucose stimulation, as compared to controls. Grafts of co-microencapsulated Sertoli's cells with islets resulted in prolongation of the achieved normoglycemia in the animals receiving Sertoli's cells with islets as compared to controls that received islets only. Sertoli's cells do promote mitogenic activities upon in vitro co-incubation with islets, whose in vitro functional and in vivo post-transplant consequences were evident. Sertoli's cells could, therefore, be co-microencapsulated with islets for transplantation in diabetic recipients. 相似文献
48.
Tyramine and dopamine are taken up by rat platelets through the serotonin uptake mechanism while phenethylamine is not taken up. This indicates that an aromatic hydroxyl group is a structural requirement for the uptake of phenethylamine derivatives by rat platelets. Although none of these phenethylamine derivatives induce platelet shape change, they inhibit serotonin-induced shape change and serotonin uptake with the same relative potency (). This suggests that the receptors controlling serotonin uptake and serotonin-induced shape change have a common structural component that binds phenethylamine derivatives. However, the fact that phenethylamine derivatives activate the serotonin uptake mechanism but do not induce platelet shape change suggests that serotonin uptake and serotonin-induced shape change are mediated by two distinct activation sites of serotonin receptors. 相似文献
49.
Darren Griffith Sara Cecco Ennio Zangrando Alberta Bergamo Gianni Sava Celine J. Marmion 《Journal of biological inorganic chemistry》2008,13(4):511-520
Reaction of 3-pyridinehydroxamic acid and 4-pyridinehydroxamic acid (3-pyha and 4-pyha) with either [NBu4][RuCl4(dmso-S)2] or [(dmso)2H][RuCl4(dmso-S)2] (dmso is dimethyl sulfoxide) in acetone afforded three new ruthenium(III) dimethyl sulfoxide pyridinehydroxamic acid complexes:
[NBu4][trans-RuCl4(dmso-S)(4-pyha)]·CH3COCH3 (1), [3-pyhaH][trans-RuCl4(dmso-S)(3-pyha)] (2) and [4-pyhaH][trans-RuCl4(dmso-S)(4-pyha)] (3). The solid-state structure of [NBu4][trans-RuCl4(dmso-S)(4-pyha)]·CH3COCH3 (1) was determined by X-ray crystallography. 2 and 3 were pharmacologically evaluated for their in vitro cytotoxicity, their ability to inhibit cell invasion and their gelatinase
activity. 2 and 3 were devoid of cytotoxicity against the cell lines tested. 2 inhibited invasion of the highly invasive MDA-MB-231 cells to a much greater extent than 3. Contrary to expectations, neither 2 nor 3 had any inhibitory effect on matrix metalloproteinase (MMP) production and/or activity and in fact 3 was found to enhance the production and/or activity of both MMP-2 and MMP-9. 相似文献
50.
The distinctive nucleus of kainoid amino acids, (2S,3R)-(+)-2-carboxypyrrolidine-3-acetic acid 6, was synthesized by a chemoenzymatic process, exploiting the diastereomeric cis/trans methyl pyroglutamate derivatives 10a-c/11a-c as key intermediates. These mixtures, when subjected to a kinetic resolution mediated by α-chymotrypsin, reacted diastereo-, regio-, and enantioselectively to give the trans derivatives (+)-10a-c possessing the correct (2S,3R) configuration. Subsequently, the desired product (2S,3R)-(+)-6 could be obtained after well-established transformations. 相似文献