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31.
32.
Narumon Sereekhajornjaru Chanat Somboon Roonglawan Rattanajak William A. Denny Prapin Wilairat Saranya Auparakkitanon 《Acta tropica》2014
The hematin-targeting properties of pynacrine, an acridine analog of the schizontocidal antimalarial drug, pyronaridine, were evaluated to probe the role of the latter's benzonaphthyridine moiety. Pynacrine was as active as pyronaridine in inhibiting glutathione-induced hematin degradation and in enhancing hematin-mediated membrane lysis. It formed a 1:2 complex with hematin but was 50-fold less effective in inhibiting β-hematin formation. However, pynacrine was as potent as pyronaridine in inhibiting intra-erythrocytic Plasmodium falciparum growth in culture, suggesting that it has other off-target(s) effects. 相似文献
33.
R. E. Foulger P. Denny J. Hardy M. J. Martin T. Sawford R. C. Lovering 《Neuroinformatics》2016,14(3):297-304
The Gene Ontology (GO) is widely recognised as the gold standard bioinformatics resource for summarizing functional knowledge of gene products in a consistent and computable, information-rich language. GO describes cellular and organismal processes across all species, yet until now there has been a considerable gene annotation deficit within the neurological and immunological domains, both of which are relevant to Parkinson’s disease. Here we introduce the Parkinson’s disease GO Annotation Project, funded by Parkinson’s UK and supported by the GO Consortium, which is addressing this deficit by providing GO annotation to Parkinson’s-relevant human gene products, principally through expert literature curation. We discuss the steps taken to prioritise proteins, publications and cellular processes for annotation, examples of how GO annotations capture Parkinson’s-relevant information, and the advantages that a topic-focused annotation approach offers to users. Building on the existing GO resource, this project collates a vast amount of Parkinson’s-relevant literature into a set of high-quality annotations to be utilized by the research community. 相似文献
34.
Robert S. Gibson Denny D. Watson Blase A. Carabello Nina D. Holt George A. Beller 《The American journal of cardiology》1982,49(7):1586-1593
To determine the prevalence and clinical significance of increased lung thallium-201 uptake during submaximal exercise myocardial scintigraphy performed 2 weeks after acute myocardial infarction, 61 patients underwent submaximal exercise testing (target heart rate, 120 beats/min), multigated blood pool imaging at rest and coronary angiography before hospital discharge. Thallium lung uptake on the initial anterior projection image was graded qualitatively by comparing the intensity of thallium-201 activity in the lungs with that in the mediastinum. In 39 patients (64 percent), it was normal (equal to mediastinal activity) and in 22 (36 percent), it was increased (greater than mediastinal activity). Compared with patients with normal lung uptake, those with increased uptake had a greater prevalence of prior infarction (13 versus 36 percent, probability [p] < 0.05), less global cardiac reserve as assessed by the four level New York Heart Association classification (p < 0.05), more advanced Killip class in the coronary care unit (p < 0.05), a higher Norris coronary prognostic index (2.6 ± 1.9 versus 4.6 ± 2.3 [mean ± standard deviation], p <0.01), failure to achieve the target heart rate because of dyspnea, fatigue or angina (36 versus 86 percent, p < 0.01), a greater prevalence of exercise-induced S-T segment depression (18 versus 45 percent, p < 0.05), a greater number of anterior thallium-201 myocardlal defects (p < 0.05); a lower radionuclide ejection fraction at rest (50.4 ± 6.1 versus 39.6 ± 9.3 percent, p < 0.01) and a greater number of asynergic left ventricular segments (p < 0.05).Thus, the occurrence of increased lung thallium-201 uptake during submaximal exercise scintigraphy in the early postinfarction period is frequent and appears to be a marker of severe and functionally more important coronary artery disease associated with left ventricular dysfunction. 相似文献
35.
Denny John Prabir Chatterjee Shruti Murthy Ramesh Bhat Baba Maiyaki Musa 《The Indian journal of tuberculosis》2018,65(3):208-217
Background
In India, multidrug-resistant tuberculosis (MDR-TB) patients are usually treated in hospitals. Decentralised care model, however, has been suggested as a possible alternative by the World Health Organization (WHO). In the “End TB Strategy”, the WHO highlights, as one of the key targets for 2035, that ‘no TB-affected families should face catastrophic hardship due to the tuberculosis’. Removal of financial barriers to health-care access and mitigation of catastrophic expenditures are therefore considered vital to achieve the universal health coverage (UHC) goal. Since forgoing healthcare due to the financial constraints is a known fact in India, decentralised care as an intervention choice (as against hospital-based care) might enhance equity provided it is an affordable choice. Thus, an economic evaluation was conducted, from the perspective of the national health system in India, to assess the cost-effectiveness of decentralised care compared to centralised care for MDR-TB.Methods
This study uses a decision-analytic model with a follow-up of two years to assess the expected costs of the decentralised versus the centralised approaches for MDR-TB treatment. A published systematic review of observational studies yielded the MDR-TB treatment outcomes, which included treatment success, treatment default, treatment failure, and mortality parameters. It was observed that these parameters did not vary significantly between the two alternatives. Treatment costs included the following costs: hospital admission costs, clinic costs, visits to laboratory and MDR-TB centre, drug therapy, injections and food. Costs data of drugs, diagnosis, hospital stay and travel to public facilities, based on a simple market survey, were taken from a recently published study on MDR-TB expenditures in the Chhattisgarh state of India. Potential cost savings related to the implementation of decentralised MDR-TB care for all patients who initiated MDR-TB treatment in India were additionally estimated.Results
Estimated average expected total treatment cost was US$ 3390.56 for the hospital-based model and US$ 1724.1 for the decentralised model for a patient treated for MDR-TB in India, generating potential savings of US$1666.50 per case, with ICER US$ 2382.68 per QALY gained. One of the primary drivers of this difference was the significantly more intensive (thus expensive) stay charges in the hospital. If the costs and treatment probabilities are extrapolated to the whole country, with 48114 MDR-TB patients initiated on treatment in 2017, decentralised care would have additional 1058 patients cured, gain additional 3824 QALYs, and avert 2165 deaths, as compared to centralised care, in India. At various scenarios of coverage rates of decentralised and centralised care the cost difference would range between 23% and 94% for the country.Conclusion
Our study provides evidence of cost savings for MDR-TB patients if patients choose decentralised treatment in comparison to suggested hospitalisation of these patients for centralised treatment with similar outcomes. The economic evaluation presented in this study expected significant efficiency gains in choice of two treatment options and the cost savings may improve equity. In India, treatment of MDR-TB using decentralised care is expected to result in similar patient outcomes at markedly reduced public health costs compared with centralised care. 相似文献36.
37.
Susana Gavidia‐Payne Bianca Denny Kate Davis Andrew Francis Merv Jackson 《Clinical Psychologist》2015,19(3):111-121
The substantial focus of resilience research on childhood well‐being has resulted in limited knowledge regarding other aspects of resilience in families, such as that of parents. Informed by literature in childhood and family resilience, in this review, we progress conceptual understanding by focusing on parental resilience. The definition of parental resilience, as the capacity of parents to deliver a competent and quality level of parenting to children despite the presence of risk factors, is offered here as a worthwhile framework through which to explore variables thought to contribute to resilience among parents. A conceptual model is proposed whereby parental psychological well‐being and self‐efficacy, family functioning, and social connectedness are specifically addressed, with each posited as playing an important role in parents’ ability to deliver high‐quality parenting. In addition to these factors, how parents accommodate adversity and find meaning in their everyday lives within their families is hypothesised to be an important process in understanding parental resilience. 相似文献
38.
39.
Hua Xu Melinda C Aldrich Qingxia Chen Hongfang Liu Neeraja B Peterson Qi Dai Mia Levy Anushi Shah Xue Han Xiaoyang Ruan Min Jiang Ying Li Jamii St Julien Jeremy Warner Carol Friedman Dan M Roden Joshua C Denny 《J Am Med Inform Assoc》2015,22(1):179-191
Objectives Drug repurposing, which finds new indications for existing drugs, has received great attention recently. The goal of our work is to assess the feasibility of using electronic health records (EHRs) and automated informatics methods to efficiently validate a recent drug repurposing association of metformin with reduced cancer mortality.Methods By linking two large EHRs from Vanderbilt University Medical Center and Mayo Clinic to their tumor registries, we constructed a cohort including 32 415 adults with a cancer diagnosis at Vanderbilt and 79 258 cancer patients at Mayo from 1995 to 2010. Using automated informatics methods, we further identified type 2 diabetes patients within the cancer cohort and determined their drug exposure information, as well as other covariates such as smoking status. We then estimated HRs for all-cause mortality and their associated 95% CIs using stratified Cox proportional hazard models. HRs were estimated according to metformin exposure, adjusted for age at diagnosis, sex, race, body mass index, tobacco use, insulin use, cancer type, and non-cancer Charlson comorbidity index.Results Among all Vanderbilt cancer patients, metformin was associated with a 22% decrease in overall mortality compared to other oral hypoglycemic medications (HR 0.78; 95% CI 0.69 to 0.88) and with a 39% decrease compared to type 2 diabetes patients on insulin only (HR 0.61; 95% CI 0.50 to 0.73). Diabetic patients on metformin also had a 23% improved survival compared with non-diabetic patients (HR 0.77; 95% CI 0.71 to 0.85). These associations were replicated using the Mayo Clinic EHR data. Many site-specific cancers including breast, colorectal, lung, and prostate demonstrated reduced mortality with metformin use in at least one EHR.Conclusions EHR data suggested that the use of metformin was associated with decreased mortality after a cancer diagnosis compared with diabetic and non-diabetic cancer patients not on metformin, indicating its potential as a chemotherapeutic regimen. This study serves as a model for robust and inexpensive validation studies for drug repurposing signals using EHR data. 相似文献
40.
Heart Failure Reviews - Cardiac involvement occurs in light-chain (AL), transthyretin wild-type (wtATTR), and hereditary (hATTR) amyloidosis; other types of amyloidosis account... 相似文献