全文获取类型
收费全文 | 6055篇 |
免费 | 383篇 |
国内免费 | 45篇 |
专业分类
耳鼻咽喉 | 29篇 |
儿科学 | 152篇 |
妇产科学 | 167篇 |
基础医学 | 1004篇 |
口腔科学 | 79篇 |
临床医学 | 501篇 |
内科学 | 1589篇 |
皮肤病学 | 276篇 |
神经病学 | 584篇 |
特种医学 | 142篇 |
外科学 | 447篇 |
综合类 | 11篇 |
一般理论 | 2篇 |
预防医学 | 357篇 |
眼科学 | 36篇 |
药学 | 376篇 |
中国医学 | 26篇 |
肿瘤学 | 705篇 |
出版年
2024年 | 6篇 |
2023年 | 54篇 |
2022年 | 149篇 |
2021年 | 209篇 |
2020年 | 118篇 |
2019年 | 174篇 |
2018年 | 200篇 |
2017年 | 131篇 |
2016年 | 151篇 |
2015年 | 203篇 |
2014年 | 257篇 |
2013年 | 300篇 |
2012年 | 464篇 |
2011年 | 526篇 |
2010年 | 286篇 |
2009年 | 240篇 |
2008年 | 399篇 |
2007年 | 389篇 |
2006年 | 423篇 |
2005年 | 374篇 |
2004年 | 351篇 |
2003年 | 305篇 |
2002年 | 291篇 |
2001年 | 34篇 |
2000年 | 22篇 |
1999年 | 42篇 |
1998年 | 57篇 |
1997年 | 58篇 |
1996年 | 49篇 |
1995年 | 46篇 |
1994年 | 33篇 |
1993年 | 32篇 |
1992年 | 16篇 |
1991年 | 16篇 |
1990年 | 12篇 |
1989年 | 17篇 |
1988年 | 13篇 |
1987年 | 5篇 |
1986年 | 5篇 |
1985年 | 3篇 |
1984年 | 6篇 |
1983年 | 3篇 |
1981年 | 5篇 |
1980年 | 4篇 |
1979年 | 1篇 |
1977年 | 4篇 |
排序方式: 共有6483条查询结果,搜索用时 234 毫秒
61.
62.
BACKGROUND AND PURPOSE: To appraise the potential benefit of a conformal technique with non-coplanar fields to minimise lung irradiation in the radiation treatment of breast. PATIENTS AND METHODS: A comparative study was carried out at planning level for six patients selected for their inadequate sparing of healthy lung tissue with the reference tangential technique. Plans were designed for the conventional tangential technique, for an alternative conformal approach with three beams and for the newly proposed technique with two non-coplanar beams. RESULTS: In average for the new technique compared to the reference, mean lung dose dropped from approximately 16 to 10.5 Gy, V(20 Gy) from 29.5 to 18.2% and the dose delivered to 1/3 (1/4) of the lung volume dropped from 28.5% (67.3%) to 8.7% (13.4%). For PTV, the volume receiving at least 90% of the prescribed dose resulted 97.4% for the new and 97.3% for the reference. Conformity index improved significantly from 2.58 for the reference to 1.84 for the new technique. CONCLUSIONS: For a subgroup population of breast cancer patients, where conventional techniques failed to achieve high conformal avoidance, a treatment modality with non-coplanar beams was developed and clinically tested for six patients. It resulted dosimetrically adequate, particularly when the risk of toxicity is relevant. 相似文献
63.
Pierfrancesco Tassone Paola Neri Renate Burger Rocco Savino Masood Shammas Laurence Catley Klaus Podar Dharminder Chauhan Serena Masciari Antonella Gozzini Pierosandro Tagliaferri Salvatore Venuta Nikhil C Munshi Kenneth C Anderson 《Clinical cancer research》2005,11(11):4251-4258
Interleukin-6 (IL-6) protects multiple myeloma cells against apoptosis induced by glucocorticoids. Here, we investigated whether inhibition of the IL-6 signaling pathway by the IL-6 receptor superantagonist Sant7 enhances the in vivo antitumor effects of dexamethasone on the IL-6-dependent multiple myeloma cell line INA-6. For this purpose, we used a novel murine model of human multiple myeloma in which IL-6-dependent INA-6 multiple myeloma cells were directly injected into human bone marrow implants in severe combined immunodeficient (SCID) mice (SCID-hu). The effect of in vivo drug treatments on multiple myeloma cell growth was monitored by serial determinations of serum levels of soluble IL-6 receptor (shuIL-6R), which is released by INA-6 cells and served as a marker of tumor growth. In SCID-hu mice engrafted with INA-6 cells, treatment with either Sant7 or dexamethasone alone did not induce significant reduction in serum shuIL-6R levels. In contrast, the combination of Sant7 with dexamethasone resulted in a synergistic reduction in serum shuIL-6R levels after 6 consecutive days of treatment. Gene expression profiling of INA-6 cells showed down-regulation of proliferation/maintenance and cell cycle control genes, as well as up-regulation of apoptotic genes in multiple myeloma cells triggered by Sant7 and dexamethasone combination. In vitro colony assays showed inhibition of myeloid and erythroid colonies from normal human CD34(+) progenitors in response to dexamethasone, whereas Sant7 neither inhibited colony growth nor potentiated the inhibitory effect of dexamethasone. Taken together, these results indicate that inhibition of IL-6 signaling by Sant7 significantly potentiates the therapeutic action of dexamethasone against multiple myeloma cells, providing the preclinical rationale for clinical trials of Sant7 in combination with dexamethasone to improve patient outcome in multiple myeloma. 相似文献
64.
Debora Soncini Claudia Martinuzzi Pamela Becherini Elisa Gelli Samantha Ruberti Katia Todoerti Luca Mastracci Paola Contini Antonia Cagnetta Antonella Laudisi Fabio Guolo Paola Minetto Maurizio Miglino Sara Aquino Riccardo Varaldo Daniele Reverberi Matteo Formica Mario Passalacqua Alessio Nencioni Antonino Neri Mehmet K. Samur Nikhil C. Munshi Mariateresa Fulciniti Roberto M. Lemoli Michele Cea. 《Haematologica》2022,107(6):1410
65.
Silvia Bianchi Maria Gori Clara Fappani Giulia Ciceri Marta Canuti Daniela Colzani Marco Dura Mara Terraneo Anna Lamberti Melissa Baggieri Sabrina Senatore Marino Faccini Fabio Magurano Elisabetta Tanzi Antonella Amendola 《Viruses》2022,14(5)
Despite the existence of an effective live-attenuated vaccine, measles can appear in vaccinated individuals. We investigated breakthrough measles cases identified during our surveillance activities within the measles/rubella surveillance network (MoRoNet) in Milan and surrounding areas (Northern Italy). Between 2017 and 2021, we confirmed measles virus (genotypes B3 or D8) infections in 653 patients and 51 of these (7.8%) were vaccinees. Among vaccinated individuals whose serum was available, a secondary failure was evidenced in 69.4% (25/36) of cases while 11 patients (30.6%) were non-responders. Non-responders were more frequently hospitalized and had significantly lower Ct values in both respiratory and urine samples. Median age and time since the last immunization were similar in the two groups. Importantly, we identified onward transmissions from vaccine failure cases. Vaccinees were involved in 20 outbreaks, in 10 of them they were able to transmit the virus, and in 8 of them, they were the index case. Comparing viral hemagglutinin sequences from vaccinated and non-vaccinated subjects did not show a specific mutation pattern. These results suggest that vaccination failure was likely due to the poor immune response of single individuals and highlights the importance of identifying breakthrough cases and characterizing their clinical and virologic profiles. 相似文献
66.
Alessandra Andrisani Gabriella Donà Chiara Sabbadin Stefano Dall'Acqua Elena Tibaldi Antonella Roveri 《Gynecological endocrinology》2017,33(12):928-932
Endometriosis, an estrogen-dependent chronic gynecological disease in women of reproductive age, is characterized by a systemic inflammation status involving also red blood cells (RBCs). In this study, we evaluated how the protein oxidative status could be involved in the worsening of RBC conditions due to dapsone intake in endometriotic women in potential treatment for skin or infection diseases. Blood samples from two groups of volunteers, control group (CG) and endometriosis patient group (PG), were analyzed for their content of band 3 tyrosine phosphorylation (Tyr-P) and high molecular weight aggregate (HMWA) in membranes, and glutathione (GSH) content and carbonic anhydrase (CA) activity in cytosol. In endometriotic patients, RBC showed the highest level of oxidative-related alterations both in membrane and cytosol. More interestingly, the addition of dapsone hydroxylamine (DDS-NHOH) could induce further increase of both membranes and cytosol markers, with an enhancement of CA activity reaching about 66% of the total cell enzyme amount. In conclusion, in PG the systemic inflammatory status leads to the inability of counteracting adjunctive oxidative stress, with a potential involvement of CA-related pathologies, such as glaucoma. Hence, the importance of the evaluation of therapeutic approaches worsening oxidative imbalance present in PG RBC is underlined. 相似文献
67.
Dana Schneider Mariangela Vicarioto Serelina Coluzzi Antonella Matteocci Nicoletta Revelli Barbara Foglieni Patrizia Artusi Donatella Londero Anna Quaglietta Giancarla Barrotta Domenico Visceglie Giuseppina Portararo Jonella Gilsdorf 《Trasfusione del sangue》2022,20(4):329
BackgroundABO antibody titres are important in many clinical decisions; however, much variability is observed in titre results. For reliable and reproducible titre results, automated ABO titration methods have been developed. In this 10-site study, we evaluated the equivalency of the automated ABO titration assays on the Galileo NEO, a fully automated blood bank analyzer (Immucor, Inc.) to manual titration with gel Column Agglutination Technology (CAT), as well as the reproducibility of both methods.Materials and methodsTen different locations participated in this study. The equivalency study included 70 random samples at each site. The reproducibility study tested the same blinded 30-sample panel at each study site. Anti-A and anti-B IgM and IgG antibody titres were tested with both the automated and manual methods; additionally, dithiothreitol (DTT) treatment was used to inactivate IgM antibodies in the manual CAT method.ResultsThe equivalency between CAT manual method and Galileo NEO automated titres at each site ranged from 38 to 88%; equivalency for each isotype was 66.2% for IgM, 60.6% for IgG, and 88.5% for DTT-treated IgG. The reproducibility study evaluated the titre variation of each sample obtained from the 10 sites. The average titre ranges (in doubling dilutions) for the automated and manual methods, respectively, were 2.15±1.0 and 4.03±1.8 for IgM, and 1.53±0.7 and 4.10±1.9 for IgG; for the manual DTT-treated IgG, the average titre range was 3.45±1.8 doubling dilutions.DiscussionThe results demonstrated that the Galileo NEO automated and manual CAT ABO titres are not equivalent. However, the study also demonstrated that titre reproducibility is enhanced with the Galileo NEO automated ABO titration assays relative to the manual CAT ABO titration method. Therefore, to improve management of patients receiving care across multiple institutions, our study supports the use of automated ABO titration. 相似文献
68.
69.
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70.
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