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81.
A fluorescent curcumin-based Zn(II)-complex reactivates mutant (R175H and R273H) p53 in cancer cells
Alessia Garufi Daniela Trisciuoglio Manuela Porru Carlo Leonetti Antonella Stoppacciaro Valerio D’Orazi Maria Laura Avantaggiati Alessandra Crispini Daniela Pucci Gabriella D’Orazi 《Journal of experimental & clinical cancer research : CR》2013,32(1):72
Background
Mutations of the p53 oncosuppressor gene are amongst the most frequent aberration seen in human cancer. Some mutant (mt) p53 proteins are prone to loss of Zn(II) ion that is bound to the wild-type (wt) core, promoting protein aggregation and therefore unfolding. Misfolded p53 protein conformation impairs wtp53-DNA binding and transactivation activities, favouring tumor growth and resistance to antitumor therapies. Screening studies, devoted to identify small molecules that reactivate mtp53, represent therefore an attractive anti-cancer therapeutic strategy. Here we tested a novel fluorescent curcumin-based Zn(II)-complex (Zn-curc) to evaluate its effect on mtp53 reactivation in cancer cells.Methods
P53 protein conformation was examined after Zn-curc treatment by immunoprecipitation and immunofluorescence assays, using conformation-specific antibodies. The mtp53 reactivation was evaluated by chromatin-immunoprecipitation (ChIP) and semi-quantitative RT-PCR analyses of wild-type p53 target genes. The intratumoral Zn-curc localization was evaluated by immunofluorescence analysis of glioblastoma tissues of an ortothopic mice model.Results
The Zn-curc complex induced conformational change in p53-R175H and -R273H mutant proteins, two of the most common p53 mutations. Zn-curc treatment restored wtp53-DNA binding and transactivation functions and induced apoptotic cell death. In vivo studies showed that the Zn-curc complex reached glioblastoma tissues of an ortothopic mice model, highlighting its ability to crossed the blood-tumor barrier.Conclusions
Our results demonstrate that Zn-curc complex may reactivate specific mtp53 proteins and that may cross the blood-tumor barrier, becoming a promising compound for the development of drugs to halt tumor growth. 相似文献82.
G. Decorti Luigi Candussio Fiora Bartoli Klugmann Antonella Strohmayer Maria Pia Mucci Alessandro Mosco Luciano Baldini 《Cancer chemotherapy and pharmacology》1997,40(4):363-366
It has been proven that the anthracyclines induce an important, noncytotoxic histamine release from rat peritoneal mast cells.
As mast cells derived from different tissues exhibit marked heterogeneity, the effect of Adriamycin in comparison with other
antineoplastic agents was tested on fragments of the right heart auricle, which contain a great number of mast cells. In this
experimental model, Adriamycin induced a dose-dependent histamine release that was significantly limited by the antiexocytotic
drug sodium cromoglycate. The antineoplastic agents cisplatin and 5-fluorouracil, in contrast, did not provoke any comparable
histamine release. In the formulation employed in clinical settings, paclitaxel was also capable of inducing a histamine release
comparable with that of Adriamycin; the exocytotic activity, however, was also evident when the tissue fragments were treated
with Cremophor EL alone, without the addition of paclitaxel, whereas treatment of samples with paclitaxel dissolved in ethanol
did not induce any releasing action. These data thus suggest that the secretory activity should be ascribed to the solvent
Cremophor EL and not to paclitaxel. The release of histamine induced by paclitaxel in Cremophor EL/ethanol was also limited
by sodium cromoglycate. These results again indicate that histamine release from mast cells derived not only from the peritoneal
cavity but also from the cardiac tissue could play a role in the cardiotoxicity of anthracyclines and of paclitaxel in the
clinically employed formulation.
Received: 18 August 1996 / Accepted: 22 December 1996 相似文献
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Cecilia Fazio Laura Daprai Arianna Neri Marcello Tirani Paola Vacca Milena Arghittu Luigina Ambrosio Danilo Cereda Maria Gramegna Annapina Palmieri Anna Carannante Maria Rosa Bertoli Lucia Crottogini Giorgio Gennati Eugenia Quinz Livia Trezzi Andrea Ciammaruconi Silvia Fillo Antonella Fortunato Giovanni Rezza Florigio Lista Paola Stefanelli 《Euro surveillance : bulletin européen sur les maladies transmissibles = European communicable disease bulletin》2022,27(24)
In Italy, serogroup C meningococci of the clonal complex cc11 (MenC/cc11) have caused several outbreaks of invasive meningococcal disease (IMD) during the past 20 years. Between December 2019 and January 2020, an outbreak of six cases of IMD infected with MenC/cc11 was identified in a limited area in the northern part of Italy. All cases presented a severe clinical picture, and two of them were fatal. This report is focused on the microbiological and molecular analysis of meningococcal isolates with the aim to reconstruct the chain of transmission. It further presents the vaccination strategy adopted to control the outbreak. The phylogenetic evaluation demonstrated the close genetic proximity between the strain involved in this outbreak and a strain responsible for a larger epidemic that had occurred in 2015 and 2016 in the Tuscany Region. The rapid identification and characterisation of IMD cases and an extensive vaccination campaign contributed to the successful control of this outbreak caused by a hyperinvasive meningococcal strain. 相似文献
87.
Xiang Li Chun-Hao Huang Francisco J. Snchez-Rivera Margaret C. Kennedy Darjus F. Tschaharganeh John P. Morris IV Antonella Montinaro Kevin P. O'Rourke Ana Banito John E. Wilkinson Chi-Chao Chen Yu-Jui Ho Lukas E. Dow Sha Tian Wei Luan Elisa de Stanchina Tinghu Zhang Nathanael S. Gray Henning Walczak Scott W. Lowe 《Proceedings of the National Academy of Sciences of the United States of America》2022,119(17)
88.
Milena Villarini Sara Levorato Tania Salvatori Elisabetta Ceretti Sara Bonetta Annalaura Carducci Tiziana Grassi Samuele Vannini Francesco Donato Silvia Bonetta Marco Verani Antonella de Donno Silvia Bonizzoni Alberto Bonetti Massimo Moretti Umberto Gelatti 《International journal of hygiene and environmental health》2018,221(6):883-892
Background
Recent data support the hypothesis that genetic damage occurring early in life during childhood can play an important role in the development of chronic diseases in adulthood, including cancer.Objectives
The objective of this paper, part of the MAPEC_LIFE project, is to describe the frequency of micronuclei and meta-nuclear alterations in exfoliated buccal cells of 6–8year-old Italian children recruited in five Italian towns (i.e., Brescia, Torino, Pisa, Perugia and Lecce) with different air pollution levels.Methods
About 200 children per town were recruited from primary schools. Biological samples were collected twice from the same children, in two different seasons (winter 2014-15 and late spring 2015). Cytogenetic damage was evaluated by the buccal micronucleus cytome assay.Results
Overall,n?=?1046 children represent the final cohort of the MAPEC_LIFE study. On the whole, the results showed a higher mean MN frequency in winter (0.42?±?0.54‰) than late-spring (0.22?±?0.34‰). MN frequency observed among the five Italian towns showed a trend that follows broadly the levels of air pollution in Italy: the highest MN frequency was observed in Brescia during both seasons, the lowest in Lecce (winter) and Perugia (late-spring).Conclusions
To the best of our knowledge, the number of recruited children included in the analysis (n?=?1046) is the highest compared to previous studies evaluating the frequency of MN in exfoliated buccal cells so far. MN frequency was associated with winter season and living in towns at various levels of air pollution, suggesting an important role of this exposure in determining early cytogenetic effects. 相似文献89.
Emmanuel de Billy Marsha Pellegrino Domenico Orlando Giulia Pericoli Roberta Ferretti Pietro Businaro Maria Antonietta Ajmone-Cat Sabrina Rossi Lucia Lisa Petrilli Nicola Maestro Francesca Diomedi-Camassei Marco Pezzullo Cristiano De Stefanis Paola Bencivenga Alessia Palma Rossella Rota Francesca Del Bufalo Luca Massimi Gerrit Weber Chris Jones Andrea Carai Simona Caruso Biagio De Angelis Ignazio Caruana Concetta Quintarelli Angela Mastronuzzi Franco Locatelli Maria Vinci 《Neuro-oncology》2022,24(7):1150
BackgroundDiffuse midline gliomas (DMG) H3K27M-mutant, including diffuse intrinsic pontine glioma (DIPG), are pediatric brain tumors associated with grim prognosis. Although GD2-CAR T-cells demonstrated significant anti-tumor activity against DMG H3K27M-mutant in vivo, a multimodal approach may be needed to more effectively treat patients. We investigated GD2 expression in DMG/DIPG and other pediatric high-grade gliomas (pHGG) and sought to identify chemical compounds that would enhance GD2-CAR T-cell anti-tumor efficacy.MethodsImmunohistochemistry in tumor tissue samples and immunofluorescence in primary patient-derived cell lines were performed to study GD2 expression. We developed a high-throughput cell-based assay to screen 42 kinase inhibitors in combination with GD2-CAR T-cells. Cell viability, western blots, flow-cytometry, real time PCR experiments, DIPG 3D culture models, and orthotopic xenograft model were applied to investigate the effect of selected compounds on DIPG cell death and CAR T-cell function.ResultsGD2 was heterogeneously, but widely, expressed in the tissue tested, while its expression was homogeneous and restricted to DMG/DIPG H3K27M-mutant cell lines. We identified dual IGF1R/IR antagonists, BMS-754807 and linsitinib, able to inhibit tumor cell viability at concentrations that do not affect CAR T-cells. Linsitinib, but not BMS-754807, decreases activation/exhaustion of GD2-CAR T-cells and increases their central memory profile. The enhanced anti-tumor activity of linsitinib/GD2-CAR T-cell combination was confirmed in DIPG models in vitro, ex vivo, and in vivo.ConclusionOur study supports the development of IGF1R/IR inhibitors to be used in combination with GD2-CAR T-cells for treating patients affected by DMG/DIPG and, potentially, by pHGG. 相似文献
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