全文获取类型
收费全文 | 3046篇 |
免费 | 155篇 |
国内免费 | 26篇 |
专业分类
耳鼻咽喉 | 25篇 |
儿科学 | 89篇 |
妇产科学 | 78篇 |
基础医学 | 502篇 |
口腔科学 | 36篇 |
临床医学 | 227篇 |
内科学 | 809篇 |
皮肤病学 | 40篇 |
神经病学 | 399篇 |
特种医学 | 83篇 |
外科学 | 224篇 |
综合类 | 9篇 |
预防医学 | 152篇 |
眼科学 | 33篇 |
药学 | 202篇 |
中国医学 | 10篇 |
肿瘤学 | 309篇 |
出版年
2024年 | 10篇 |
2023年 | 29篇 |
2022年 | 57篇 |
2021年 | 97篇 |
2020年 | 54篇 |
2019年 | 57篇 |
2018年 | 104篇 |
2017年 | 77篇 |
2016年 | 68篇 |
2015年 | 95篇 |
2014年 | 111篇 |
2013年 | 160篇 |
2012年 | 239篇 |
2011年 | 227篇 |
2010年 | 125篇 |
2009年 | 139篇 |
2008年 | 234篇 |
2007年 | 220篇 |
2006年 | 206篇 |
2005年 | 186篇 |
2004年 | 204篇 |
2003年 | 152篇 |
2002年 | 141篇 |
2001年 | 23篇 |
2000年 | 15篇 |
1999年 | 26篇 |
1998年 | 34篇 |
1997年 | 29篇 |
1996年 | 18篇 |
1995年 | 10篇 |
1994年 | 19篇 |
1993年 | 16篇 |
1992年 | 8篇 |
1991年 | 4篇 |
1990年 | 3篇 |
1989年 | 6篇 |
1988年 | 5篇 |
1987年 | 4篇 |
1986年 | 5篇 |
1985年 | 1篇 |
1984年 | 4篇 |
1983年 | 3篇 |
1982年 | 1篇 |
1977年 | 1篇 |
排序方式: 共有3227条查询结果,搜索用时 15 毫秒
31.
32.
Tampellini M Berruti A Bitossi R Gorzegno G Alabiso I Bottini A Farris A Donadio M Sarobba MG Manzin E Durando A Defabiani E De Matteis A Ardine M Castiglione F Danese S Bertone E Alabiso O Massobrio M Dogliotti L 《Breast cancer research and treatment》2006,98(3):241-248
Summary Tumor response to first-line chemotherapy in advanced breast cancer offers prognostic information and may be used as a surrogate marker for evaluating treatment efficacy. With this study we wanted to determine whether changes in circulating serum CA 15-3 levels during chemotherapy provided additional information for prognostic prediction. Serum CA 15-3 was measured at baseline and after 3 and 6 months during anthracycline-based first-line chemotherapy in 526 patients with advanced breast cancer prospectively enrolled in five phase II-III trials. Changes in marker levels were correlated with disease response, time to progression and overall survival. In all, 336 patients attained a disease response. A significant relationship was found between disease response and CA 15-3 variations, although many individual discrepancies were also observed. At the 6-month time point, the median time to progression was 15.3 months in patients with normal marker levels throughout the study, 11.7 months in those with a CA15-3 reduction >25%, 9.6 months in those with elevated baseline CA 15-3 levels which did not change during therapy and 8.6 months in those with increased marker levels (p < 0.001). The median survival was 42.3, 29.7, 28.5, and 24.8 months, respectively (p < 0.002). The prognostic role of changes in CA 15-3 levels was maintained in the patient subset attaining disease response or stabilization to treatment (p < 0.001) and after adjusting for clinical response and major prognostic parameters in the multivariate analysis (p < 0.001). In conclusion, monitoring serum CA 15-3 levels during first-line chemotherapy in advanced breast cancer patients provides prognostic information independently from tumor response. 相似文献
33.
Targeting of the tumor stroma, including the tumor vasculature, represents a new frontier in the treatment of malignancy.
Preclinical studies and clinical experiences have established that stroma-directed novel agents must be combined with conventional
therapies in order to achieve relevant therapeutic efficacy. Here we review our preclinical experience on combinations of
paclitaxel with a tyrosine kinase receptor inhibitor of angiogenesis (SU6668) and a vascular disrupting agent (VDA, ZD6126),
and discuss the critical factors that determine the outcome of these treatments. We also analyze the relevance of the intrinsic
sensitivity of the tumor to the drugs, as well as the possibility that the two combined agents synergistically affect the
vasculature or independently target the host and the tumor compartments. Finally, we discuss the need to carefully optimize
scheduling and sequencing, through the use of reliable end points, in order to avoid negative pharmacological interactions
and to improve the antineoplastic efficacy of paclitaxel-based combination treatments. 相似文献
34.
Malnutrition is one of the main factors determining cachexia syndrome, which negatively impacts the quality of life and survival. In cancer patients, artificial nutrition is considered as an appropriate therapy when the impossibility of an adequate oral intake worsened nutritional and clinical conditions. This study aims to verify, in a home palliative care setting for cancer patients, if home artificial nutrition (HAN) supplies a patient’s energy requirement, improving nutritional and performance status. A nutritional service team performed counseling at a patient’s home and assessed nutritional status (body mass index, weight loss in the past 6 months), resting energy expenditure (REE), and oral food intake; Karnofsky Performance Status (KPS); cachexia degree; and survival. From 1990 to 2021, 1063 patients started HAN. Among these patients, 101 suspended artificial nutrition for oral refeeding. Among the 962 patients continuing HAN until death, 226 patients (23.5%) survived 6 weeks or less. HAN allowed to achieve a positive energy balance in 736 patients who survived more than 6 weeks, improving body weight and KPS when evaluated after 1 month of HAN. Advanced cancer and cachexia degree at the entry of the study negatively affected the positive impact of HAN. 相似文献
35.
Gennaro Daniele Clorinda Schettino Laura Arenare Domenico Bilancia Fabio Farinati Piera Federico Stefano Tamberi Gino Crivellari Sandro Barni Raffaella Tortora Francesco Izzo Antonio Frassoldati Luigi Cavanna Claudia Mucciarini Luigi Bolondi Angelo Dinota Filippo Pelizzaro Maria Carmela Piccirillo Piera Gargiulo Massimo Di Maio Ciro Gallo Francesco Perrone Bruno Daniele 《肝癌研究(英文版)》2021,7(7):52-65
Aim: Only patients with good liver function {[Child-Pugh (CP)] A class} were eligible for trials testing sorafenib as first-line treatment of hepatocellular car... 相似文献
36.
Cyclosporin A in the ocular fluids of uveitis patients following long-term systemic administration 总被引:1,自引:0,他引:1
Paolo Mora Uta Ceglarek Francesca Manzotti Laura Zavota Arturo Carta Raffaella Aldigeri Jelka G. Orsoni 《Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie》2008,246(7):1047-1052
BACKGROUND/AIMS: To determine the levels of cyclosporin A (CsA) in tears and the anterior segment of the eye following long-term oral intake for autoimmune diseases. METHODS: Subjects taking oral CsA to treat relapsing autoimmune ocular inflammation were included in this study. All of the patients had been quiescent for at least 6 months. In patients scheduled for cataract extraction (group A), the CsA levels in the blood, aqueous humour and anterior capsule of the lens were determined. In subjects not requiring surgical intervention (group B), CsA was measured in tears and blood. The samples were analysed using turbulent flow chromatography coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS). RESULTS: There were 19 subjects in group A and 43 subjects in group B. CsA was detectable in all of the tear samples with a mean value of 22.4 +/- 20.2 ng/ml and there was a significant positive correlation between the CsA levels in tears and blood (P = 0.012). CsA was not detected in any of the surgical samples. CONCLUSION: LC-MS/MS proved very sensitive for detecting CsA in low-volume biological samples. CsA was present in human tears in proportion to the blood level after an average of 12 hours from the last oral intake. 相似文献
37.
Domenica Giannandrea Natalia Platonova Michela Colombo Mara Mazzola Valentina Citro Raffaella Adami Filippo Maltoni Silvia Ancona Vincenza Dolo Ilaria Giusti Andrea Basile Anna Pistocchi Laura Cantone Valentina Bollati Lavinia Casati Elisabetta Calzavara Mauro Turrini Elena Lesma Raffaella Chiaramonte 《Haematologica》2022,107(9):2183
Multiple myeloma (MM) is an incurable hematologic neoplasm, whose poor prognosis is deeply affected by the propensity of tumor cells to localize in the bone marrow (BM) and induce the protumorigenic activity of normal BM cells, leading to events associated with tumor progression, including tumor angiogenesis, osteoclastogenesis, and the spread of osteolytic bone lesions. The interplay between MM cells and the BM niche does not only rely on direct cell-cell interaction, but a crucial role is also played by MM-derived extracellular vesicles (MM-EV). Here, we demonstrated that the oncogenic NOTCH receptors are part of MM-EV cargo and play a key role in EV protumorigenic ability. We used in vitro and in vivo models to investigate the role of EV-derived NOTCH2 in stimulating the protumorigenic behavior of endothelial cells and osteoclast progenitors. Importantly, MM-EV can transfer NOTCH2 between distant cells and increase NOTCH signaling in target cells. MM-EV stimulation increases endothelial cell angiogenic ability and osteoclast differentiation in a NOTCH2-dependent way. Indeed, interfering with NOTCH2 expression in MM cells may decrease the amount of NOTCH2 also in MM-EV and affect their angiogenic and osteoclastogenic potential. Finally, we demonstrated that the pharmacologic blockade of NOTCH activation by γ-secretase inhibitors may hamper the biological effect of EV derived by MM cell lines and by the BM of MM patients. These results provide the first evidence that targeting the NOTCH pathway may be a valid therapeutic strategy to hamper the protumorigenic role of EV in MM as well as other tumors. 相似文献
38.
Raffaella Lucchini Ciro Franzese Suela Vukcaj Giorgio Purrello Denis Panizza Valeria Faccenda Stefano Andreoli Gian Luca Poli Davide Baldaccini Lorenzo Lo Faro Stefano Tomatis Luigi Franco Cazzaniga Marta Scorsetti Stefano Arcangeli 《Current oncology (Toronto, Ont.)》2022,29(12):9349
Background: The aim of this study was to investigate the feasibility of ultrahypofractionated radiotherapy to the prostate bed in patients with biochemical and/or clinical relapse following radical prostatectomy who were enrolled in the prospective, observational, multicentric POPART trial (). Methods: Patients with post-radical prostatectomy PSA levels of ≥0.1–2.0 ng/mL and/or local relapse at PSMA PET/CT or multiparametric MRI were treated with Linac-based SBRT on the prostate bed up to a total dose of 32.5 Gy in five fractions every other day (EQD21.5 = 74.2 Gy). Maximum acute toxicity was assessed using the Common Terminology Criteria for Adverse Events version 5 scale. International Consultation on Incontinence Questionnaire—Short Form (ICIQ-SF) and Prostate Cancer Index Composite for Clinical Practice (EPIC-CP) scores were assessed at baseline and during the follow-up. Results: From April 2021 to June 2022, thirty men with a median age of 72 years (range 55–82) were enrolled in three centers. The median PSA level before RT was 0.30 ng/mL (range 0.18–1.89 ng/mL). At 3 months post-treatment, no GI or ≥2 GU side effects were reported; three patients (10%) experienced Grade 1 GU toxicity. No changes in ICIQ-SF or in the urinary domains of EPIC-CP were observed, while a transient worsening was registered in the bowel domain. At the same time point, all but two patients, who progressed distantly, were found to be biochemically controlled with a median post-treatment PSA level of 0.07 ng/mL (range 0–0.48 ng/mL). Conclusions: Our preliminary findings show that SBRT can be safely extended to the postoperative setting, without an increase in short-term toxicity or a significant decline in QoL. Long-term results are needed to confirm this strategy. NCT04831970相似文献
39.
Delli Pizzi Andrea Caposiena Daniele Mastrodicasa Domenico Trebeschi Stefano Lambregts Doenja Rosa Consuelo Cianci Roberta Seccia Barbara Sessa Barbara Di Flamminio Filippo Maria Chiacchiaretta Piero Caravatta Luciana Cinalli Sebastiano Di Sebastiano Pierluigi Caulo Massimo Genovesi Domenico Beets-Tan Regina Basilico Raffaella 《Abdominal imaging》2019,44(11):3595-3605
Abdominal Radiology - To compare tumor detectability and conspicuity of standard b = 1000 s/mm2 (b1000) versus ultrahigh b = 2000 s/mm2 (b2000)... 相似文献
40.
Migration of V delta 1 and V delta 2 T cells in response to CXCR3 and CXCR4 ligands in healthy donors and HIV-1-infected patients: competition by HIV-1 Tat 总被引:3,自引:0,他引:3 下载免费PDF全文
Poggi A Carosio R Fenoglio D Brenci S Murdaca G Setti M Indiveri F Scabini S Ferrero E Zocchi MR 《Blood》2004,103(6):2205-2213
We show that HIV-1-infected patients have increased concentrations of circulating V delta 1 T cells (2.2%-9.0% of T lymphocytes; healthy donors, 1.0%-2%) and, in some instances, V delta 2 T cells (3.5%-4.8% vs 2.0%-3.3%). In these patients, both V delta 1 and V delta 2 T cells are CXCR3+CXCR4+, whereas in healthy donors CXCR4 was preferentially expressed on V delta 1 T lymphocytes. gamma delta T cells transmigrated across endothelial monolayers, in response to interferon-gamma-inducing protein-10 (IP-10/CXCL10), stromal cell-derived factor-1 (SDF-1/CXCL12), or both, according to the expression of the specific receptors CXCR3 and CXCR4. Interestingly, 6Ckine/SLC/CCL21 was more effective than IP-10/CXCL10 on V delta 1 CXCR3+ cells, whereas V delta 2 CXCR3+ cells were driven more efficiently by IP-10/CXCL10. IP-10/CXCL10- and SDF-1/CXCL12-induced transmigration was dependent on phosphoinositide-3 kinase (PI-3K), as demonstrated by the use of the specific blockers wortmannin and LY294002 and by the activation of the downstream serine kinase Akt/PKB on ligation of CXCR3 and CXCR4. Occupancy of CXCR3, but not of CXCR4, led to CAMKII activation; accordingly, the CAMKII inhibitors KN62 and KN93 decreased IP-10/CXCL10- but not SDF-1/CXCL12-driven transmigration. Finally, HIV-1 Tat, which is present in the serum of HIV-1-infected patients, interferes with the chemotactic activity of these chemokines because of the cysteine-rich domain of the protein, which contains CXC and CC chemokine-like sequences. 相似文献