全文获取类型
收费全文 | 1865篇 |
免费 | 172篇 |
国内免费 | 7篇 |
专业分类
耳鼻咽喉 | 15篇 |
儿科学 | 57篇 |
妇产科学 | 45篇 |
基础医学 | 238篇 |
口腔科学 | 42篇 |
临床医学 | 221篇 |
内科学 | 330篇 |
皮肤病学 | 44篇 |
神经病学 | 230篇 |
特种医学 | 46篇 |
外科学 | 224篇 |
综合类 | 15篇 |
预防医学 | 167篇 |
眼科学 | 26篇 |
药学 | 158篇 |
中国医学 | 1篇 |
肿瘤学 | 185篇 |
出版年
2023年 | 34篇 |
2022年 | 16篇 |
2021年 | 39篇 |
2020年 | 33篇 |
2019年 | 61篇 |
2018年 | 49篇 |
2017年 | 57篇 |
2016年 | 69篇 |
2015年 | 62篇 |
2014年 | 71篇 |
2013年 | 97篇 |
2012年 | 141篇 |
2011年 | 140篇 |
2010年 | 74篇 |
2009年 | 58篇 |
2008年 | 111篇 |
2007年 | 98篇 |
2006年 | 94篇 |
2005年 | 75篇 |
2004年 | 96篇 |
2003年 | 79篇 |
2002年 | 74篇 |
2001年 | 16篇 |
2000年 | 17篇 |
1999年 | 29篇 |
1998年 | 12篇 |
1997年 | 20篇 |
1996年 | 19篇 |
1995年 | 10篇 |
1994年 | 10篇 |
1993年 | 20篇 |
1992年 | 24篇 |
1991年 | 17篇 |
1990年 | 21篇 |
1989年 | 15篇 |
1988年 | 14篇 |
1987年 | 12篇 |
1986年 | 14篇 |
1985年 | 18篇 |
1984年 | 9篇 |
1983年 | 12篇 |
1982年 | 5篇 |
1981年 | 7篇 |
1979年 | 13篇 |
1978年 | 18篇 |
1977年 | 9篇 |
1976年 | 8篇 |
1975年 | 5篇 |
1970年 | 5篇 |
1963年 | 5篇 |
排序方式: 共有2044条查询结果,搜索用时 375 毫秒
81.
Hiroko Morisaki Gretchen MacCarrick Mark Lindsay David Liang Sarju G. Mehta Jennifer Hague Judith Verhagen Ingrid van de Laar Marja Wessels Yvonne Detisch Mieke van Haelst Annette Baas Klaske Lichtenbelt Kees Braun Denise van der Linde Jolien Roos‐Hesselink George McGillivray Josephina Meester Isabelle Maystadt Paul Coucke Elie El‐Khoury Sandhya Parkash Birgitte Diness Lotte Risom Ingrid Scurr Yvonne Hilhorst‐Hofstee Takayuki Morisaki Julie Richer Julie Désir Marlies Kempers Andrea L. Rideout Gabrielle Horne Chris Bennett Elisa Rahikkala Geert Vandeweyer Maaike Alaerts Aline Verstraeten Hal Dietz Lut Van Laer Bart Loeys 《Human mutation》2018,39(5):621-634
The Loeys–Dietz syndrome (LDS) is a connective tissue disorder affecting the cardiovascular, skeletal, and ocular system. Most typically, LDS patients present with aortic aneurysms and arterial tortuosity, hypertelorism, and bifid/broad uvula or cleft palate. Initially, mutations in transforming growth factor‐β (TGF‐β) receptors (TGFBR1 and TGFBR2) were described to cause LDS, hereby leading to impaired TGF‐β signaling. More recently, TGF‐β ligands, TGFB2 and TGFB3, as well as intracellular downstream effectors of the TGF‐β pathway, SMAD2 and SMAD3, were shown to be involved in LDS. This emphasizes the role of disturbed TGF‐β signaling in LDS pathogenesis. Since most literature so far has focused on TGFBR1/2, we provide a comprehensive review on the known and some novel TGFB2/3 and SMAD2/3 mutations. For TGFB2 and SMAD3, the clinical manifestations, both of the patients previously described in the literature and our newly reported patients, are summarized in detail. This clearly indicates that LDS concerns a disorder with a broad phenotypical spectrum that is still emerging as more patients will be identified. All mutations described here are present in the corresponding Leiden Open Variant Database. 相似文献
82.
Olesen M Skov V Mechta M Mumm BH Rasmussen LM 《Molecular and cellular endocrinology》2012,362(1-2):149-156
The aim of this study was to examine the effects of the OPG-RANKL-TRAIL system on proliferation, regulation of calcification-associated genes and calcification of human vascular smooth muscle cells (HVSMCs). Small interfering (si)RNA-mediated knockdown of OPG was followed by treatment of HVSMCs with recombinant RANKL or TRAIL. Regulation of a calcification-associated gene set was assayed by pathway analysis of microarray results. The lack of OPG in HVSMCs or treatment with RANKL or TRAIL did not affect proliferation of HVSMCs. In addition, OPG, RANKL or TRAIL did not modify the regulation of a calcification-associated gene set. Finally, in the long term calcification assay, we found that cells isolated from seven different human donors showed a great variability in the response to RANKL and insulin. However, overall RANKL and/or insulin did not affect the development of calcification of HVSMCs. These studies indicate that OPG knockdown does not alter the calcification process in HVSMCs. 相似文献
83.
C. Frederiksen J. Lykke Ib J. Christensen N. Brünner H. J. Nielsen 《Scandinavian journal of clinical and laboratory investigation》2013,73(5):545-552
Objective. Tissue inhibitor of metalloproteinase‐1 (TIMP‐1) plays a major role in the regulation of tissue growth, including cancer growth. The TIMP‐1 protein can be determined in plasma, and increased plasma levels of TIMP‐1 are associated with a poor prognosis of colorectal cancer patients. The aim of the present study was to evaluate whether tumour tissue release of the TIMP‐1 protein contributes to the increased plasma levels of TIMP‐1 observed in patients with colorectal cancer. Material and methods. Preoperative blood samples from a peripheral vein and intraoperative blood samples from a tumour artery, a tumour vein and from a peripheral vein were drawn from 24 patients undergoing elective, intended curative surgery for primary rectal cancer. TIMP‐1 levels were determined concurrently in plasma from all samples using a validated ELISA method. Counts of white blood cells and platelets were also carried out. Results. No significant differences between plasma TIMP‐1 levels could be demonstrated in any compartment. In particular, there was no significant difference in TIMP‐1 levels in plasma from tumour arteries and tumour veins. However, there was a significant decrease in neutrophil cell counts from tumour arteries to tumour veins (p<0.001). Conclusions. The present results do not support the current hypothesis that tumour cells contribute substantially to increased plasma TIMP‐1 levels observed in patients with colorectal cancer. 相似文献
84.
Karin A. W. Wadt Anne-Marie Gerdes Thomas V. O. Hansen Birgitte G. Toft Lennart Friis-Hansen Mette K. Andersen 《Familial cancer》2012,11(3):535-537
Hereditary papillary renal carcinoma (HPRC) is a highly penetrant hereditary renal cancer syndrome caused by germline missense mutations in the c-MET proto-oncogene. HPRC is clinically characterized by multiple bilateral papillary renal-cell carcinomas. Here we report a family with a novel missense mutation in c-MET. The original pathology report of four primary kidney cancers (1988–1997) revealed renal-cell carcinoma. A revised report described multiple adenomas and papillary renal-cell carcinomas with focal clear cells and a mixture of type 1 and type 2 pattern, emphasizing the importance of revised pathology examinations in possible hereditary renal-cell carcinomas especially when described before 1997. 相似文献
85.
Dorte Smidt Lis Andersen Torpet Birgitte Nauntofte Karen Margrethe Heegaard Anne Marie Lynge Pedersen 《Community dentistry and oral epidemiology》2010,38(5):422-435
Smidt D, Torpet LA, Nauntofte B, Heegaard KM, Pedersen AML. Associations between labial and whole salivary flow rates, systemic diseases and medications in a sample of older people. Community Dent Oral Epidemiol 2010; 38: 422–435. © 2010 John Wiley & Sons A/S Abstract – Objective: To investigate the associations between age, gender, systemic diseases, medications and labial and whole salivary flow rates in older people. Methods: Unstimulated labial (LS) and unstimulated (UWS) and chewing‐stimulated (SWS) whole salivary flow rates were measured in 389 randomly selected community‐dwelling Danish women and 279 men aged 65–97 years. Systemic diseases, medications (coded according to the Anatomical Therapeutic Chemical (ATC) Classification System), tobacco and alcohol consumption were registered. Results: The number of diseases and medications was higher and UWS lower in the older age groups. On average, women were slightly older, had more diseases, higher medication intake and lower UWS, SWS and LS than men. High number of diseases and medications was associated with low UWS, SWS and LS. In the healthy (14%) and nonmedicated (19%) participants, flow rates were not associated with age and gender, apart from SWS being lower in nonmedicated women. Low UWS were associated with psychiatric and respiratory disorders, type 2 diabetes and intake of psycholeptics, psychoanaleptics (especially SRRIs), respiratory agents, oral antidiabetics (particularly sulfonylureas), magnesium‐hydroxide, cardiac agents, quinine, thiazides, calcium channel blockers, statins, urinary antispasmodics, glucosamine, NSAIDs, opioids and ophthalmologicals. SWS were lower in participants with ophthalmological disorders using ophthalmologicals (especially antiglaucoma agents and miotics), but also in those taking antidepressants, cardiac agents (mostly digitalis glycosides) and calcium channel blockers. Cardiovascular diseases and intake of anti‐thrombotics (mainly low dose aspirins), calcium channel blockers and oral antidiabetics were associated with low LS. Conclusions: In older people, low salivary flow rates are associated with specific and high number of diseases and medications, but neither with age and gender per se nor with tobacco and alcohol consumption. Low UWS are associated with more diseases and medications than SWS and LS, which were primarily associated with cardiovascular diseases and medications including preventive agents such as low‐dose aspirins and statins. New insights into medications and their association with salivary gland function were achieved using the ATC classification system. 相似文献
86.
87.
Mette Holst RN MCN PhD Henrik H Rasmussen MD PhD Birgitte S Laursen RN MSc Nursing PhD 《Scandinavian journal of caring sciences》2011,25(1):176-184
Scand J Caring Sci; 2011; 25; 176–184 Can the patient perspective contribute to quality of nutritional care? Aim: Undernutrition has been seen in hospitalized patients at all times. Nurses have a central position in the nutritional care of the patient. Despite guidelines for nutritional practise and care, 20–55% of patients are still at risk of complications to insufficient nutrition intake. The aim of this study was to obtain knowledge of hospitalized patient’s experiences of being undernourished, to understand implications this might have to quality of nutritional nursing care. Methods: Qualitative interviews were undertaken in 12 hospitalized patients at severe nutritional risk. Findings: Pain, no appetite, bad taste and side effects to medication were among reasons for poor eating. Nurses practically did not address or question symptoms that could influence poor eating and were only to a low degree involved at patient initiative. The patients appeared to divide into two groups; One ‘Passive group’, characterized with fatigue, lack of concentration and short term memory, were found insusceptible to increase nutrition intake by motivation and guidance. The overall motivation in the other ‘Active’ group was the setting of and achievement of goals, which had to be clear, communicated and followed up by nurses and physicians. This group furthermore found self‐determination and active involvement determinant for a positive and fruitful cooperation between staff and themselves. Conclusions: Nurses were in progressive about clarifying why patients did not eat. Patients highly regarded nutrition registration when followed up, however, this was only practised to a low degree. Severely undernourished patients could be divided in two groups. The ‘Passive group’ should be attended to systematically. Artificial nutrition is often needed in this group. The ‘Active group’ should be cared for with individual, active involvement from nurses. Nurses should be able to distinct which nutritional care for which patient, and act upon it. 相似文献
88.
89.
90.
Lisa J Frederiksen Richard Sullivan Lori R Maxwell Shannyn K Macdonald-Goodfellow Michael A Adams Brian M Bennett D Robert Siemens Charles H Graham 《Clinical cancer research》2007,13(7):2199-2206
PURPOSE: Hypoxia contributes to drug resistance in solid cancers, and studies have revealed that low concentrations of nitric oxide (NO) mimetics attenuate hypoxia-induced drug resistance in tumor cells in vitro. Classic NO signaling involves activation of soluble guanylyl cyclase, generation of cyclic GMP (cGMP), and activation of cGMP-dependent protein kinase. Here, we determined whether chemosensitization by NO mimetics requires cGMP-dependent signaling and whether low concentrations of NO mimetics can chemosensitize tumors in vivo. EXPERIMENTAL DESIGN: Survival of human prostate and breast cancer cells was assessed by clonogenic assays following exposure to chemotherapeutic agents. The effect of NO mimetics on tumor chemosensitivity in vivo was determined using a mouse xenograft model of human prostate cancer. Drug efflux in vitro was assessed by measuring intracellular doxorubicin-associated fluorescence. RESULTS: Low concentrations of the NO mimetics glyceryl trinitrate (GTN) and isosorbide dinitrate attenuated hypoxia-induced resistance to doxorubicin and paclitaxel. Similar to hypoxia-induced drug resistance, inhibition of various components of the NO signaling pathway increased resistance to doxorubicin, whereas activation of the pathway with 8-bromo-cGMP attenuated hypoxia-induced resistance. Drug efflux was unaffected by hypoxia and inhibitors of drug efflux did not significantly attenuate hypoxia-induced chemoresistance. Compared with mice treated with doxorubicin alone, tumor growth was decreased in mice treated with doxorubicin and a transdermal GTN patch. The presence of GTN and GTN metabolites in plasma samples was confirmed by gas chromatography. CONCLUSION: Tumor hypoxia induces resistance to anticancer drugs by interfering with endogenous NO signaling and reactivation of NO signaling represents a novel approach to enhance chemotherapy. 相似文献