全文获取类型
收费全文 | 6059篇 |
免费 | 460篇 |
国内免费 | 56篇 |
专业分类
耳鼻咽喉 | 26篇 |
儿科学 | 133篇 |
妇产科学 | 114篇 |
基础医学 | 946篇 |
口腔科学 | 103篇 |
临床医学 | 580篇 |
内科学 | 1578篇 |
皮肤病学 | 103篇 |
神经病学 | 732篇 |
特种医学 | 153篇 |
外科学 | 508篇 |
综合类 | 14篇 |
一般理论 | 1篇 |
预防医学 | 381篇 |
眼科学 | 65篇 |
药学 | 489篇 |
中国医学 | 13篇 |
肿瘤学 | 636篇 |
出版年
2024年 | 6篇 |
2023年 | 66篇 |
2022年 | 158篇 |
2021年 | 268篇 |
2020年 | 131篇 |
2019年 | 166篇 |
2018年 | 231篇 |
2017年 | 166篇 |
2016年 | 187篇 |
2015年 | 244篇 |
2014年 | 276篇 |
2013年 | 315篇 |
2012年 | 530篇 |
2011年 | 549篇 |
2010年 | 273篇 |
2009年 | 243篇 |
2008年 | 432篇 |
2007年 | 451篇 |
2006年 | 385篇 |
2005年 | 381篇 |
2004年 | 322篇 |
2003年 | 324篇 |
2002年 | 244篇 |
2001年 | 31篇 |
2000年 | 13篇 |
1999年 | 17篇 |
1998年 | 30篇 |
1997年 | 25篇 |
1996年 | 23篇 |
1995年 | 14篇 |
1994年 | 15篇 |
1993年 | 12篇 |
1992年 | 8篇 |
1991年 | 11篇 |
1990年 | 7篇 |
1989年 | 3篇 |
1988年 | 4篇 |
1987年 | 1篇 |
1986年 | 1篇 |
1985年 | 1篇 |
1984年 | 1篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1980年 | 1篇 |
1979年 | 1篇 |
1971年 | 1篇 |
1970年 | 1篇 |
1969年 | 3篇 |
1918年 | 1篇 |
排序方式: 共有6575条查询结果,搜索用时 17 毫秒
51.
During the last century, the reduction of birth and all-cause mortality rates have resulted in an increase in the life expectancy and the proportion of the elderly population in many countries. For example, elderly women represent more than 16% and elderly men comprise more than 12% of the population in Italy. The health consequences of these demographic shifts in population is important, because older people experience reductions in some physiologic functions and in increased incidence of chronic, mainly cardiovascular, diseases. Data derived from a survey of men between the ages of 71 and 91 years, who are the survivors of the original rural samples of the Italian section of the Seven Countries Study, show the large contribution of cardiovascular diseases to the long list of chronic conditions. The indicators of self-sufficiency, dementia, and of the self-perception of poor health proved much more common among subjects with cardiovascular diseases than in those with other chronic conditions. 相似文献
52.
Claudio Pintus Carlo Manzoni Simona Nappo Luigi Perrelli 《Pediatric surgery international》1993,8(2):109-112
In a review of 15 pediatric patients who had ingested caustic substances, the authors describe the diagnostic and therapeutic procedures to be followed as well as the complications that may occur with their use. The cases reported include 1 esophageal rupture caused by balloon dilatation and 1 recurrent stenosis treated with a silastic tutor. 相似文献
53.
Soluble CD40 ligand plasma levels in lung cancer. 总被引:7,自引:0,他引:7
Mario Roselli Tommaso C Mineo Stefania Basili Francesca Martini Sabrina Mariotti Simona Aloe Girolamo Del Monte Vincenzo Ambrogi Antonella Spila Raffaele Palmirotta Roberta D'Alessandro Giovanni Davì Fiorella Guadagni Patrizia Ferroni 《Clinical cancer research》2004,10(2):610-614
PURPOSE: Tumor-induced platelet activation may cause the release of various cytokines, including CD40 ligand (CD40L). Activation of the CD40/CD40L pathway in human tumors may result in thrombin generation, which is known to be involved in angiogenesis. Thus, we investigated whether soluble (s)CD40L levels are increased in patients with lung cancer as a result of platelet and/or coagulation activation. EXPERIMENTAL DESIGN: Citrated plasma samples were obtained from 120 patients with different stages and histotypes of lung cancer and 60 age- and sex-matched control subjects. sCD40L, sP-selectin (marker of platelet activation), prothrombin fragment 1 + 2, and thrombin-antithrombin III complex levels (both markers of coagulative activation) were measured in all samples. RESULTS: Patients with lung cancer had median sCD40L levels higher than in control subjects (0.46 versus 0.13 ng/ml; P < 0.0001), although correlation with the stage of disease was not evident. Nonetheless, sCD40L levels were significantly higher in squamous cancer compared with adenocarcinoma (0.75 versus 0.27 ng/ml; P < 0.05). Moreover, median sCD40L levels were higher in stage IV compared with nonmetastatic squamous lung cancer (1.02 versus 0.61 ng/ml; P < 0.05). sCD40L levels significantly correlated with sP-selectin (P < 0.001), prothrombin fragment 1 + 2 (P < 0.001), or thrombin-antithrombin III complex (P < 0.05) in squamous lung cancer, but only sP-selectin (P = 0.011) was independently related to sCD40L. CONCLUSIONS: These findings indicate that elevated sCD40L levels can be preferentially found in patients with advanced squamous cancer and provide evidence that increased levels of this cytokine are associated to the occurrence of in vivo platelet activation. 相似文献
54.
55.
In vitro and in vivo interaction between cisplatin and topotecan in ovarian carcinoma systems 总被引:7,自引:0,他引:7
Simona Romanelli Paola Perego Graziella Pratesi Nives Carenini Monica Tortoreto Franco Zunino 《Cancer chemotherapy and pharmacology》1998,41(5):385-390
Topotecan, a camptothecin analogue, is a␣specific inhibitor of topoisomerase I approved for use in the treatment of patients
with refractory ovarian carcinoma. The drug's mechanism of action suggests a potential efficacy of drug combinations incorporating
DNA-damaging agents. In an attempt better to define a␣rational basis for drug combination we examined the effect of topotecan
on the cytotoxicity and antitumor activity of cisplatin in an ovarian carcinoma system growing in vitro and in vivo as a tumor
xenograft. The in vitro cell system included a cisplatin-sensitive cell line, IGROV-1, and a cisplatin-resistant subline,
IGROV-1/Pt0.5, which is characterized by p53 mutation and loss of normal function of the wild-type gene of the parental cell
line. This cell system was chosen since the cell sensitivity to DNA-damaging agents appears to be dependent on p53 gene status.
Cytotoxicity was assessed by the growth inhibition assay using different schedules: (a) a 1-h period of cisplatin exposure
followed by a 24-h topotecan treatment and (b) a 1-h period of simultaneous exposure to cisplatin and topotecan. In the case
of the sequential schedule, an additive interaction was observed in IGROV-1 and IGROV-1/Pt0.5 cells. When the simultaneous
schedule was used, a synergistic interaction, more evident for the cisplatin-sensitive cells, was found. On the basis of these
observations at a cellular level, the effect of concomitant administration of the two drugs (i.e., the most favorable schedule)
was studied in the IGROV-1 tumor xenograft, which is moderately responsive to cisplatin and topotecan. Suboptimal doses of
each drug (with a low dose of topotecan, 5.1 mg/kg) achieved an antitumor effect comparable with or superior to that of the
optimal dose of a single treatment (tumor weight inhibition, 60%), thus indicating a␣pharmacological advantage of the combination
over the single treatment. However, an increase in the topotecan dose (7.1 mg/kg) was associated with an evident increase
in the toxicity of the combination, thereby suggesting that the drug interaction was not tumor-specific. Although the molecular
basis of the drug interaction is not clear, it is likely that inhibition of topoisomerase I affects the ability of cells to
repair cisplatin adducts. Such findings may have pharmacological implications since they suggest the potential clinical interest
of topoisomerase I inhibitors in combination with cisplatin.
Received: 14 June 1997 / Accepted: 18 September 1997 相似文献
56.
Simona Soverini Giovanni Martinelli Gianantonio Rosti Simona Bassi Marilina Amabile Angela Poerio Barbara Giannini Elena Trabacchi Fausto Castagnetti Nicoletta Testoni Simona Luatti Antonio de Vivo Daniela Cilloni Barbara Izzo Milena Fava Elisabetta Abruzzese Daniele Alberti Fabrizio Pane Giuseppe Saglio Michele Baccarani 《Journal of clinical oncology》2005,23(18):4100-4109
PURPOSE: Point mutations within the ABL kinase domain of the BCR-ABL gene have been associated with clinical resistance to imatinib mesylate in chronic myeloid leukemia (CML) patients. To shed further light on the frequency, distribution, and prognostic significance of ABL mutations, we retrospectively analyzed a homogeneous cohort of late chronic phase CML patients who showed primary cytogenetic resistance to imatinib. PATIENTS AND METHODS: Using denaturing high-performance liquid chromatography (D-HPLC) and sequencing, we screened for ABL mutations in a total of 178 bone marrow and/or peripheral blood samples from 40 late chronic phase CML patients homogeneously treated with imatinib 400 mg/d, who did not reach a major cytogenetic response at 12 months. RESULTS: Mutations were found in 19 of 40 patients (48%). Mutations were already detectable by D-HPLC at a median of 3 months from the onset of therapy. The presence of a missense mutation was significantly associated with a greater likelihood of subsequent progression to accelerated phase/blast crisis (P = .0002) and shorter survival (P = .001). Patients carrying mutations falling within the P-loop seemed to have a particularly poor outcome in terms of time to progression (P = .032) and survival (P = .045). CONCLUSION: Our results show that, irrespective of the hematologic response, monitoring for emerging mutations in the first months of therapy may play a role in detecting patients with worse prognosis, for whom a revision of the therapeutic strategy should be considered. 相似文献
57.
Int6 expression can predict survival in early-stage non-small cell lung cancer patients. 总被引:1,自引:0,他引:1
58.
Charalampia G. Korea Giuliana Balsamo Alfredo Pezzicoli Christina Merakou Simona Tavarini Fabio Bagnoli Davide Serruto Meera Unnikrishnan 《Infection and immunity》2014,82(10):4144-4153
The opportunistic pathogen Staphylococcus aureus is one of the major causes of health care-associated infections. S. aureus is primarily an extracellular pathogen, but it was recently reported to invade and replicate in several host cell types. The ability of S. aureus to persist within cells has been implicated in resistance to antimicrobials and recurrent infections. However, few staphylococcal proteins that mediate intracellular survival have been identified. Here we examine if EsxA and EsxB, substrates of the ESAT-6-like secretion system (Ess), are important during intracellular S. aureus infection. The Esx proteins are required for staphylococcal virulence, but their functions during infection are unclear. While isogenic S. aureus esxA and esxB mutants were not defective for epithelial cell invasion in vitro, a significant increase in early/late apoptosis was observed in esxA mutant-infected cells compared to wild-type-infected cells. Impeding secretion of EsxA by deleting C-terminal residues of the protein also resulted in a significant increase of epithelial cell apoptosis. Furthermore, cells transfected with esxA showed an increased protection from apoptotic cell death. A double mutant lacking both EsxA and EsxB also induced increased apoptosis but, remarkably, was unable to escape from cells as efficiently as the single mutants or the wild type. Thus, using in vitro models of intracellular staphylococcal infection, we demonstrate that EsxA interferes with host cell apoptotic pathways and, together with EsxB, mediates the release of S. aureus from the host cell. 相似文献
59.
60.