全文获取类型
收费全文 | 492篇 |
免费 | 40篇 |
专业分类
耳鼻咽喉 | 13篇 |
儿科学 | 11篇 |
妇产科学 | 6篇 |
基础医学 | 44篇 |
口腔科学 | 2篇 |
临床医学 | 96篇 |
内科学 | 49篇 |
皮肤病学 | 6篇 |
神经病学 | 25篇 |
特种医学 | 26篇 |
外科学 | 83篇 |
综合类 | 1篇 |
预防医学 | 49篇 |
眼科学 | 6篇 |
药学 | 84篇 |
中国医学 | 2篇 |
肿瘤学 | 29篇 |
出版年
2022年 | 4篇 |
2021年 | 8篇 |
2020年 | 7篇 |
2019年 | 7篇 |
2018年 | 6篇 |
2017年 | 4篇 |
2015年 | 5篇 |
2014年 | 5篇 |
2013年 | 13篇 |
2012年 | 16篇 |
2011年 | 20篇 |
2010年 | 6篇 |
2009年 | 11篇 |
2008年 | 22篇 |
2007年 | 21篇 |
2006年 | 31篇 |
2005年 | 21篇 |
2004年 | 18篇 |
2003年 | 32篇 |
2002年 | 26篇 |
2001年 | 27篇 |
2000年 | 22篇 |
1999年 | 11篇 |
1996年 | 5篇 |
1995年 | 12篇 |
1994年 | 6篇 |
1993年 | 10篇 |
1992年 | 15篇 |
1991年 | 8篇 |
1990年 | 10篇 |
1989年 | 8篇 |
1988年 | 6篇 |
1987年 | 6篇 |
1986年 | 7篇 |
1985年 | 3篇 |
1984年 | 5篇 |
1983年 | 5篇 |
1981年 | 5篇 |
1980年 | 8篇 |
1979年 | 4篇 |
1978年 | 7篇 |
1977年 | 3篇 |
1976年 | 5篇 |
1975年 | 7篇 |
1974年 | 9篇 |
1973年 | 4篇 |
1971年 | 4篇 |
1970年 | 4篇 |
1968年 | 3篇 |
1967年 | 4篇 |
排序方式: 共有532条查询结果,搜索用时 93 毫秒
11.
Hammond TG Carlsson L Davis AS Lynch WG MacKenzie I Redfern WS Sullivan AT Camm AJ 《Cardiovascular research》2001,49(4):741-750
OBJECTIVE: To assess current practice in the pharmaceutical industry for assessing the potential for QT interval prolongation by non-cardiovascular medicinal products. METHODS: The survey was based on responses from the Toxicology and (Safety) Pharmacology laboratories (a total of 74 laboratories) of 54 companies based in Europe, Japan/Asia and the USA, received between January and March 1999. RESULTS: All 54 companies conducted preclinical in vivo electrocardiography (EGG) evaluation of new active substances (NASs). Thirty of these companies also conducted in vitro cardiac electrophysiology studies on their compounds. The majority of in vivo work was done in conscious beagle dogs. There was no consistency within the industry in defining the magnitude of change in QT interval that is considered biologically important. Most companies considered a change greater than 10% to be important, although the design of the studies suggested that group sizes used may not give sufficient statistical power to detect this size of change. Bazett's formula was used by 41% of laboratories to correct QT for changes in heart rate, despite the fact that this formula is generally deemed to be unsuitable for use in dogs. For studies in anaesthetised dogs, the majority of laboratories used barbiturate anaesthesia, but researchers should be aware of the effects of this and some other anaesthetic agents on QT interval. As for in vitro cardiac electrophysiology, there was wide diversity in the testing methodologies, particularly with regard to the test species and tissue type. As with QT prolongation, there was no consensus on the degree of action potential prolongation to cause concern. For both in vitro and in vivo testing, the majority of companies tested a minimum of three dose (or concentration) levels in order to ascertain any dose-response relationship. CONCLUSIONS: The survey provides a snapshot of the practice in the industry prior to any internationally-agreed consensus on the most effective and efficient approaches to minimising the risk of QT prolongation by new drugs in man. It must be stated that for any given methodology, the 'majority view' in the industry is not necessarily best practice. 相似文献
12.
Rabbits immunized against prostaglandins develop antibodies to prostaglandins and peptic ulcer disease (duodenal and gastric ulcers). We have evaluated the hypothesis that idiopathic gastric or duodenal ulcer disease in humans may be associated with the spontaneous occurrence of serum antibodies directed against endogenous prostaglandins. We found that serum from 45 ulcer patients (34 duodenal, 11 gastric) had a low degree of binding of radiolabeled prostaglandin E2, prostaglandin F2 alpha, or 6-keto prostaglandin F1 alpha. The extent to which prostaglandins were bound to serum of ulcer patients was not statistically different from prostaglandin binding to serum from 25 normal subjects. Therefore, we conclude that spontaneous occurrence of circulating antibodies against endogenous prostaglandins is an unlikely cause of gastroduodenal ulceration in humans. 相似文献
13.
Sputum clearance is of prime importance in the management of patients with bronchiectasis. While nebulised normal isotonic saline (0.9%) (IS) has been anecdotally used to treat patients with tenacious sputum, the use of hypertonic saline (7%) (HS) could have potential muco-protective and clearance properties. 24 patients with bronchiectasis were randomised to receive four single treatment schedules in random order: (1) active cycle breathing technique (ACBT) alone, (2) nebulised terbutaline then ACBT, (3) nebulised terbutaline, nebulised IS then ACBT and (4) nebulised terbutaline, nebulised HS then ACBT. Sputum weights were significantly higher after HS than IS (P = 0.002). Ease of expectoration also differed overall (P < 0.0001) and was significantly lower with HS than with IS (P = 0.0005). Sputum viscosity differed between treatment phases, with a significant linear trend to reduced sputum viscosity with HS (P = 0.0002). These changes were associated with small but statistically significant differences in FEV1 (P = 0.043) and FVC (P = 0.011) between treatment phases. Nebulised hypertonic saline can be used safely and effectively as an adjunct to physiotherapy in selected patients. A long-term prospective trial is now indicated to determine its effectiveness on long-term infection rate, quality of life and lung function. 相似文献
14.
15.
Oxidative phenotype protects myofibers from pathological insults induced by chronic heart failure in mice 下载免费PDF全文
Li P Waters RE Redfern SI Zhang M Mao L Annex BH Yan Z 《The American journal of pathology》2007,170(2):599-608
The fiber specificity of skeletal muscle abnormalities in chronic heart failure (CHF) has not been defined. We show here that transgenic mice (8 weeks old) with cardiac-specific overexpression of calsequestrin developed CHF (50.9% decrease in fractional shortening and 56.4% increase in lung weight, P<0.001), cachexia (37.8% decrease in body weight, P<0.001), and exercise intolerance (69.3% decrease in running distance to exhaustion, P<0.001) without a significant change in muscle fiber-type composition. Slow oxidative soleus muscle maintained muscle mass, whereas fast glycolytic tibialis anterior and plantaris muscles underwent atrophy (11.6 and 13.3%, respectively; P<0.05). In plantaris muscle, glycolytic type IId/x and IIb, but not oxidative type I and IIa, fibers displayed significant decreases in cross-sectional area (20.3%, P<0.05). Fast glycolytic white vastus lateralis muscle showed sarcomere degeneration and decreased cytochrome c oxidase IV (39.5%, P<0.01) and peroxisome proliferator-activated receptor gamma co-activator 1alpha protein expression (30.3%, P<0.01) along with a dramatic induction of the MAFbx/Atrogin-1 mRNA. These findings suggest that exercise intolerance can occur in CHF without fiber type switching in skeletal muscle and that oxidative phenotype renders myofibers resistant to pathological insults induced by CHF. 相似文献
16.
Emma Bell Frida Ponthan Claire Whitworth Deborah A. Tweddle John Lunec Christopher P. F. Redfern 《Clinical & experimental metastasis》2014,31(6):651-659
COX2 is an inducible cyclooxygenase implicated in the metastasis and migration of tumour cells. In neuroblastoma, COX2 expression has been detected in both cell lines and tumours. The treatment of neuroblastoma cells in vitro with celecoxib, a COX2 inhibitor, induces apoptosis. The aim of this study was to investigate the role of COX2 in neuroblastoma tumour biology by creating a cell line in which COX2 could be conditionally expressed. Xenograft studies showed that the conditional expression of COX2 enhanced tumour growth and malignancy. Elevated COX2 expression enhanced the proliferation and migration of neuroblastoma cells in vitro. However, elevated COX2 expression or variation between cell lines did not affect sensitivity to the COX2 inhibitor celecoxib, indicating that celecoxib does not promote cell death through COX2 inhibition. These data show that increased COX2 expression alone can enhance the tumorigenic properties of neuroblastoma cells; however, high levels of COX2 may not be a valid biomarker of sensitivity to non-steroidal anti-inflammatory drugs such as celecoxib. 相似文献
17.
Arash Mahboobin Patrick Loughlin Chris Atkeson Mark Redfern 《Medical & biological engineering & computing》2009,47(9):921-929
A key finding of human balance experiments has been that the integration of sensory information utilized for postural control
appears to be dynamically regulated to adapt to changing environmental conditions and the available sensory information, a
process referred to as “sensory re-weighting.” We propose a postural control model that includes automatic sensory re-weighting.
This model is an adaptation of a previously reported model of sensory feedback that included manual sensory re-weighting.
The new model achieves sensory re-weighting that is physiologically plausible and readily implemented. Model simulations are
compared to previously reported experimental results to demonstrate the automated sensory re-weighting strategy of the modified
model. On the whole, the postural sway time series generated by the model with automatic sensory re-weighting show good agreement
with experimental data, and are capable of producing patterns similar to those observed experimentally. 相似文献
18.
Claudia de la Cruz Gladys L. Dorantes Matías Maskin Jan S. Redfern Ricardo Romiti 《The Journal of dermatology》2017,44(1):3-12
Latin American countries view biosimilar agents as an effective approach to curtail health‐care expenditures while maintaining the safety and efficacy profile of their branded innovator comparators. To understand the complexities of the regulatory landscape and key therapeutic issues for use of biosimilars to treat moderate to severe psoriasis in Latin America, the International Psoriasis Council convened dermatology experts from Argentina, Brazil, Chile, Colombia and Mexico in October 2015 to review the definition, approval, marketing and future of biosimilars in each country and develop a consensus statement. The regulatory framework for marketing approval of biosimilars in Latin America is currently a mosaic of disparate, country‐specific, regulatory review processes, rules and standards, with considerable heterogeneity in clarity and specificity. Regulations in Argentina, Brazil, Chile and Mexico have undergone multiple refinements whereas Colombia is finalizing draft guidelines. Verification of the similarity in quality, safety and efficacy of biosimilars to the innovator biologic remains a key challenge for policy makers and regulatory authorities. Other key regulatory challenges include: naming of agents and traceability, pharmacovigilance, extrapolation of indications, and interchangeability and substitution. An urgent need exists for more Latin American countries to establish national psoriasis registries and to integrate their common components into a multinational psoriasis network, thereby enhancing their interpretative power and impact. A Latin American psoriasis network similar to PSONET in Europe would assist health‐care providers, pharmaceutical companies, regulators and patients to fully comprehend specific products being prescribed and dispensed and to identify potential regional trends or differences in safety or outcomes. 相似文献
19.
20.
Work satisfaction,stress, quality of care and morale of older people in a nursing home 总被引:1,自引:0,他引:1
The aim in the present study, which was carried out in one nursing home for older people, was to determine the feasibility of working with care workers and very frail service users to investigate links between the levels of work satisfaction and stress of the staff, and the quality of care and morale of the residents. Most of the 44 care staff (70%) and 22 cognitively intact residents (82%) participated willingly in completing rating scales through self-completion questionnaire or by interview. Well-validated scales were used to measure job satisfaction, work stress, organisational commitment, perceived quality of care, and morale and mental health. The findings revealed a staff group with a fairly high level of job dissatisfaction and stress, who were, nevertheless, very committed to the nursing home. The morale of the residents was good although the residents rated the home atmosphere lower than the staff did. Significant correlations emerged, in the expected direction, between satisfaction, commitment, stress and quality of care perceived by staff. The correlations between home atmosphere perceived by residents, and their morale and mental health were low; further investigation is needed with a larger sample. This feasibility study supports the need for further research using a case-study approach in a small number of homes because of the labour-intensive nature of the data collection and the importance of triangulating data from many sources. 相似文献