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101.
Genetic variation in UCP2 (uncoupling protein-2) is associated with energy metabolism in Pima Indians 总被引:10,自引:0,他引:10
Aims/hypothesis Uncoupling protein-2 (UCP2) is thought to play a role in insulin secretion and the development of obesity. In this study, we investigated the effects of genetic variation in UCP2 on type 2 diabetes and obesity, as well as on metabolic phenotypes related to these diseases, in Pima Indians.Methods The coding and untranslated regions of UCP2, and approximately 1 kb of the 5 upstream region, were sequenced in DNA samples taken from 83 extremely obese Pima Indians who were not first-degree relatives.Results Five variants were identified: (1) a –866G/A in the 5 upstream region; (2) a G/A in exon 2; (3) a C/T resulting in an Ala55Val substitution in exon 4; and (4, 5) two insertion/deletions (ins/del; 45-bp and 3-bp) in the 3 untranslated region. Among the 83 subjects whose DNA was sequenced, the –866G/A was in complete genotypic concordance with the Ala55Val and the 3-bp ins/del polymorphism. The G/A polymorphism in exon 2 was extremely rare. To capture the common variation in this gene for association analyses, the –866G/A variant (as a representative of Ala55Val and the 3-bp ins/del polymorphism) and the 45-bp ins/del were also genotyped for 864 full-blooded Pima Indians. Neither of these variants was associated with type 2 diabetes or body mass index. However, in a subgroup of 185 subjects who had undergone detailed metabolic measurements, these variants were associated with 24-h energy expenditure as measured in a human metabolic chamber (p=0.007 for the 45-bp ins/del and p=0.03 for the –866G/A after adjusting for age, sex, family membership, fat-free mass and fat mass).Conclusions/interpretation Our data indicate that variation in UCP2 may play a role in energy metabolism, but this gene does not contribute significantly to the aetiology of type 2 diabetes and/or obesity in Pima Indians. 相似文献
102.
Brandon P. Verdoorn MD Tamara K. Evans BS Gregory J. Hanson MD Yi Zhu PhD Larissa G. P. Langhi Prata PhD Robert J. Pignolo MD PhD Elizabeth J. Atkinson MS Erin O. Wissler-Gerdes MA George A. Kuchel MD Joan B. Mannick MD Stephen B. Kritchevsky PhD Sundeep Khosla MD Stacey A. Rizza MD Jeremy D. Walston MD Nicolas Musi MD Lewis A. Lipsitz MD Douglas P. Kiel MD Raymond Yung MB ChB Nathan K. LeBrasseur PhD Ravinder J. Singh PhD Teresa McCarthy MD MS Michael A. Puskarich MD Laura J. Niedernhofer MD PhD Paul D. Robbins PhD Matthew Sorenson JD MA Tamara Tchkonia PhD James L. Kirkland MD PhD 《Journal of the American Geriatrics Society》2021,69(11):3023-3033
The burden of senescent cells (SnCs), which do not divide but are metabolically active and resistant to death by apoptosis, is increased in older adults and those with chronic diseases. These individuals are also at the greatest risk for morbidity and mortality from SARS-CoV-2 infection. SARS-CoV-2 complications include cytokine storm and multiorgan failure mediated by the same factors as often produced by SnCs through their senescence-associated secretory phenotype (SASP). The SASP can be amplified by infection-related pathogen-associated molecular profile factors. Senolytic agents, such as Fisetin, selectively eliminate SnCs and delay, prevent, or alleviate multiple disorders in aged experimental animals and animal models of human chronic diseases, including obesity, diabetes, and respiratory diseases. Senolytics are now in clinical trials for multiple conditions linked to SnCs, including frailty; obesity/diabetes; osteoporosis; and cardiovascular, kidney, and lung diseases, which are also risk factors for SARS-CoV-2 morbidity and mortality. A clinical trial is underway to test if senolytics decrease SARS-CoV-2 progression and morbidity in hospitalized older adults. We describe here a National Institutes of Health-funded, multicenter, placebo-controlled clinical trial of Fisetin for older adult skilled nursing facility (SNF) residents who have been, or become, SARS-CoV-2 rtPCR-positive, including the rationale for targeting fundamental aging mechanisms in such patients. We consider logistic challenges of conducting trials in long-term care settings in the SARS-CoV-2 era, including restricted access, consent procedures, methods for obtaining biospecimens and clinical data, staffing, investigational product administration issues, and potential solutions for these challenges. We propose developing a national network of SNFs engaged in interventional clinical trials. 相似文献
103.
Shahar Shmuel PhD Virginia Pate MS Marc J. Pepin PharmD BCPS BCGP Janine C. Bailey PharmD BCPS Yvonne M. Golightly PT MS PhD Laura C. Hanson MD MPH Til Stürmer MD MPH PhD Rebecca B. Naumann PhD Danijela Gnjidic PhD Jennifer L. Lund PhD 《Journal of the American Geriatrics Society》2021,69(11):3212-3224
104.
Identification of an activated c-Ki-ras oncogene in rat liver tumors induced by aflatoxin B1. 总被引:2,自引:5,他引:2
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G McMahon L Hanson J J Lee G N Wogan 《Proceedings of the National Academy of Sciences of the United States of America》1986,83(24):9418-9422
Weanling male Fischer rats were administered 40 intraperitoneal injections of aflatoxin B1 (25 micrograms per animal per day) over a 2-month period. This chronic dosing regimen resulted in the sequential formation of hyperplastic foci, preneoplastic nodules, and hepatocellular carcinomas in all of the animals treated. The presence of transforming DNA sequences was detected by formation of anchorage-independent foci after transfection of tumor-derived DNA in NIH 3T3 mouse fibroblasts. Transfection of genomic DNA isolated from individual tumors from eight animals resulted in specific transforming activities ranging from 0.05 to 0.2 foci per micrograms of DNA. Primary transfectant DNAs were analyzed by Southern blot hybridization with DNA probes homologous to c-Ha-ras, c-Ki-ras, and N-ras oncogenes. A highly amplified c-Ki-ras oncogene of rat origin was detected in transformants derived from tumors in two of the eight animals tested. There was no evidence to suggest the presence of c-Ha-ras or N-ras sequences in any of the transformants. Analysis of primary liver tumor DNA showed no Ki-ras DNA amplification when compared to control liver DNA samples. Increased levels of c-Ki-ras p21 proteins were detected in 3T3 transformants containing activated rat c-Ki-ras genes. The presence of c-Ki-ras sequences of rat origin capable of inducing transformed foci can be taken as evidence that the c-Ki-ras gene has been activated in the primary liver tumors. 相似文献
105.
A Bj?rkman L Rombo M Willcox A P Hanson E Bengtsson 《Annals of tropical medicine and parasitology》1986,80(1):1-6
The efficacy of different doses of chloroquine in suppressing patent parasitaemia was investigated in 326 children two to 12 years old, living in six villages with holoendemic malaria. The children were given single doses (2, 3, 5-7 or 9-12 mg base kg-1) or a standard treatment over three days (25 mg base kg-1). Parasite prevalences were recorded after one, two, three, four, six and eight weeks. Complete clearance of Plasmodium falciparum trophozoites (TC) by day 7 was achieved by a dosage of 9-12 mg kg-1. By probit analysis of log dose response, 50% clearance (TC50) was established at about 1.5 mg kg-1, whereas a TC95 required 5.5 mg kg-1. The reappearance of patent parasitaemia was dependent on the dose of chloroquine given and on malaria transmission. After the standard dose treatment, only one re-infection in 56 children appeared within 21 days despite high sporozoite inoculation rates in the area. The dosage of 9-12 mg kg-1 yielded a hundredfold reduction of mean parasite density in the children if calculated over a four-week period. It may represent a suitable monthly regimen in a malaria control scheme in a holoendemic area with high P. falciparum sensitivity to chloroquine. 相似文献
106.
Latarsha Chisholm Sheryl Zimmerman Cherie Rosemond Eleanor McConnell Bryan J. Weiner Feng-Chang Lin Laura Hanson 《Geriatric nursing (New York, N.Y.)》2018,39(2):157-161
Nursing homes (NH) are important settings for end-of-life care, but limited implementation may impede goals of care discussions. The purpose of this study was to understand NH staff perceptions of adoption and sustainability of the Goals of Care video decision aid for families of residents with advanced dementia. Study design was a cross-sectional survey of staff at 11 NHs in North Carolina who participated in the Goals of Care (GOC) cluster randomized clinical trial. Staff perceived the GOC decision aid intervention as a positive innovation; it was perceived as more compatible with current practices by male staff, nurses, and more experienced NH staff. Perceptions were correlated with experience, implying that experience with an innovative approach may help to promote improved GOC communication in nursing homes. Nurses and social work staff could be effective champions for implementing a communication technique, like the GOC intervention. 相似文献
107.
Charles A. Austin Summer Choudhury Taylor Lincoln Lydia H. Chang Christopher E. Cox Mark A. Weaver Laura C. Hanson Judith E. Nelson Shannon S. Carson 《Journal of pain and symptom management》2018,55(3):946-952
Context
Patients triggering rapid response team (RRT) intervention are at high risk for adverse outcomes. Data on symptom burden of these patients do not currently exist, and current symptom management and communication practices of RRT clinicians are unknown.Objectives
We sought to identify the symptom experience of RRT patients and observe how RRT clinicians communicate with patients and their families.Methods
We conducted a prospective observational study from August to December 2015. Investigators attending RRT events measured frequencies of symptom assessment, communication, and supportive behaviors by RRT clinicians. As the rapid response event concluded, investigators measured patient-reported pain, dyspnea, and anxiety using a numeric rating scale of 0 (none) to 10 (most severe), with uncontrolled symptoms defined as numeric rating scale score of ≥4.Results
We observed a total of 52 RRT events. RRT clinicians assessed for pain during the event in 62% of alert patients, dyspnea in 38%, and anxiety in 21%. Goals of care were discussed during 3% of events and within 24 hours in 13%. For the primary outcome measure, at the RRT event conclusion, 44% of alert patients had uncontrolled pain, 39% had uncontrolled dyspnea, and 35% had uncontrolled anxiety.Conclusion
Hospitalized patients triggering RRT events have a high degree of uncontrolled symptoms that are infrequently assessed and treated. Although these patients experience an acute change in medical status and are at high risk for adverse outcomes, goals-of-care discussions with RRT patients or families are rarely documented in the period after the events. 相似文献108.
Rachel Dolin Pam Silberman Denise A. Kirk Sally C. Stearns Laura C. Hanson Donald H. Taylor G. Mark Holmes 《Journal of pain and symptom management》2018,55(3):775-784
Context
The rate of live discharge from hospice and the proportion of hospices exceeding their aggregate caps have both increased for the last 15 years, becoming a source of federal scrutiny. The cap restricts aggregate payments hospices receive from Medicare during a 12-month period. The risk of repayment and the manner in which the cap is calculated may incentivize hospices coming close to their cap ceilings to discharge existing patients before the end of the cap year.Objective
The objective of this work was to explore annual cap-risk trends and live discharge patterns. We hypothesized that as a hospice comes closer to exceeding its cap, a patient's likelihood of being discharged alive increases.Methods
We analyzed monthly hospice outcomes using 2012–2013 Medicare claims.Results
Adjusted analyses showed a positive and statistically significant relationship between cap risk and live discharges.Conclusion
Policymakers ought to consider the unintended consequences the aggregate cap may be having on patient outcomes of care. 相似文献109.
110.