全文获取类型
收费全文 | 3954篇 |
免费 | 182篇 |
国内免费 | 17篇 |
专业分类
耳鼻咽喉 | 22篇 |
儿科学 | 248篇 |
妇产科学 | 60篇 |
基础医学 | 438篇 |
口腔科学 | 56篇 |
临床医学 | 208篇 |
内科学 | 843篇 |
皮肤病学 | 91篇 |
神经病学 | 301篇 |
特种医学 | 126篇 |
外科学 | 455篇 |
综合类 | 413篇 |
一般理论 | 1篇 |
预防医学 | 279篇 |
眼科学 | 66篇 |
药学 | 327篇 |
1篇 | |
中国医学 | 7篇 |
肿瘤学 | 211篇 |
出版年
2022年 | 29篇 |
2021年 | 89篇 |
2020年 | 54篇 |
2019年 | 50篇 |
2018年 | 77篇 |
2017年 | 57篇 |
2016年 | 58篇 |
2015年 | 65篇 |
2014年 | 86篇 |
2013年 | 142篇 |
2012年 | 165篇 |
2011年 | 205篇 |
2010年 | 168篇 |
2009年 | 168篇 |
2008年 | 212篇 |
2007年 | 168篇 |
2006年 | 165篇 |
2005年 | 135篇 |
2004年 | 164篇 |
2003年 | 125篇 |
2002年 | 108篇 |
2001年 | 109篇 |
2000年 | 100篇 |
1999年 | 103篇 |
1998年 | 69篇 |
1997年 | 57篇 |
1996年 | 62篇 |
1995年 | 35篇 |
1994年 | 47篇 |
1992年 | 60篇 |
1991年 | 52篇 |
1990年 | 61篇 |
1989年 | 79篇 |
1988年 | 71篇 |
1987年 | 63篇 |
1986年 | 50篇 |
1985年 | 60篇 |
1984年 | 43篇 |
1983年 | 41篇 |
1981年 | 22篇 |
1980年 | 26篇 |
1979年 | 36篇 |
1978年 | 27篇 |
1977年 | 28篇 |
1976年 | 28篇 |
1975年 | 27篇 |
1974年 | 27篇 |
1973年 | 33篇 |
1972年 | 27篇 |
1971年 | 20篇 |
排序方式: 共有4153条查询结果,搜索用时 15 毫秒
101.
Vishwaratn Asthana Miel Sundararajan Ruth Linda Ackah Vivek Karun Arunima Misra Allison Pritchett Pallavi Bugga Angela Siler-Fisher William Frank Peacock 《The American journal of emergency medicine》2018,36(12):2166-2171
Background
Heart failure (HF) readmissions are a longstanding national healthcare issue for both hospitals and patients. Our purpose was to evaluate the efficacy of a structured, educational intervention targeted towards un- and under-insured emergency department (ED) HF patients.Methods
HF patients presenting to the ED for care were enrolled between July and December 2015 as part of an open label, interventional study, using a parallel observational control group. Eligible patients provided informed consent, had an established HF diagnosis, and were hemodynamically stable. Intervention patients received a standardized educational intervention in the ED waiting room before seeing the emergency physician, and a 30-day telephone follow-up. Primary and secondary endpoints were 30- and 90-day ED and hospital readmission rates, as well as days alive and out of hospital (DAOH) respectively.Results
Of the 94 patients enrolled, median age was 58.4?years; 40.4% were female, and 54.3% were African American. Intervention patients (n?=?45) experienced a 47.8% and 45.3% decrease in ED revisits (P?=?0.02 & P?<?0.001), and 60.0% and 47.4% decrease in hospital readmissions (P?=?0.049 & P?=?0.007) in the 30 and 90?days pre- versus post-intervention respectively. Control patients (n?=?49) had no change in hospital readmissions or 30-day ED revisits, but experienced a 36.6% increase in 90-day ED revisits (P?=?0.03). Intervention patients also saw a 59.2% improvement in DAOH versus control patients (P?=?0.03).Conclusion
An ED educational intervention markedly decreases ED and hospital readmissions in un- and under-insured HF patients. 相似文献102.
Ola Brodin Staffan Eksborg Marita Wallenberg Charlotte Asker-Hagelberg Erik H. Larsen Dag Mohlkert Clara Lenneby-Helleday Hans Jacobsson Stig Linder Sougat Misra Mikael Bj?rnstedt 《Nutrients》2015,7(6):4978-4994
Background: Sodium selenite at high dose exerts antitumor effects and increases efficacy of cytostatic drugs in multiple preclinical malignancy models. We assessed the safety and efficacy of intravenous administered sodium selenite in cancer patients’ refractory to cytostatic drugs in a phase I trial. Patients received first line of chemotherapy following selenite treatment to investigate altered sensitivity to these drugs and preliminary assessment of any clinical benefits. Materials and Methods: Thirty-four patients with different therapy resistant tumors received iv sodium selenite daily for consecutive five days either for two weeks or four weeks. Each cohort consisted of at least three patients who received the same daily dose of selenite throughout the whole treatment. If 0/3 patients had dose-limiting toxicities (DLTs), the study proceeded to the next dose-level. If 2/3 had DLT, the dose was considered too high and if 1/3 had DLT, three more patients were included. Dose-escalation continued until the maximum tolerated dose (MTD) was reached. MTD was defined as the highest dose-level on which 0/3 or 1/6 patients experienced DLT. The primary endpoint was safety, dose-limiting toxic effects and the MTD of sodium selenite. The secondary endpoint was primary response evaluation. Results and Conclusion: MTD was defined as 10.2 mg/m2, with a calculated median plasma half-life of 18.25 h. The maximum plasma concentration of selenium from a single dose of selenite increased in a nonlinear pattern. The most common adverse events were fatigue, nausea, and cramps in fingers and legs. DLTs were acute, of short duration and reversible. Biomarkers for organ functions indicated no major systemic toxicity. In conclusion, sodium selenite is safe and tolerable when administered up to 10.2 mg/m2 under current protocol. Further development of the study is underway to determine if prolonged infusions might be a more effective treatment strategy. 相似文献
103.
104.
Acquired granular pool defect in stored platelets 总被引:1,自引:0,他引:1
Platelets stored as concentrates (PC) for 72 h at 22 degrees C develop a functional defect. Alterations in adenine nucleotides of platelets have been shown to affect platelet function. Adenine nucleotide content of platelets was measured before and after storage and a decrease of 27.1 /+- 1.7% (mean /+- SE) in ATP and 39.1 /+- 2.6% in ADP were found in 34 PC stored with final volume of 50 ml. In 11 PC with 30 ml volume. ATP and ADP decreased by 39.4 /+- 3.2% and 49.4 /+- 2.1%, respectively. The mean ATP to ADP ratio of stored platelets was significantly higher than of fresh platelets in both groups, suggesting a relatively greater decrease in granular than metabolic pool nucleotides. Levels of low affinity platelet factor 4 measured by radioimmunoassay in plasma from 0.86 /+- 0.08 microgram/ml in the fresh PC to 8.59 /+- 0.39 microgram/ml in stored PC, indicating a concomitant alpha-granular secretion. Labeling of metabolic pool with 14C-adenine revealed a mean decrease in the adenylate energy charge of 2.0 /+- 0.4% in 12 of 16 stored PC, with a lower ATP and higher hypoxanthine labeling in stored as compared to fresh platelets. These observations suggest that stored platelets develop an acquired defect in both dense and alpha granules and in their ability to maintain ATP homeostasis. 相似文献
105.
Sulforaphane, a cruciferous isothiocyanate compound, upregulates cytoprotective genes in liver, but its effects on antioxidants and phase 2 defenses in vascular cells are unknown. Here we report that incubation of rat aortic smooth muscle A10 cells with sulforaphane (0.25-5 muM) resulted in concentration-dependent induction of a spectrum of important cellular antioxidants and phase 2 enzymes, including superoxide dismutase (SOD), catalase, the reduced form of glutathione (GSH), glutathione peroxidase, glutathione reductase (GR), glutathione S-transferase (GST), and NAD(P)H:quinone oxidoreductase 1 (NQO1). Sulforaphane also increased levels/activities of SOD, catalase, GSH and GST in isolated mitochondria of aortic smooth muscle cells. Time-dependent sulforaphane-induced increases in the mRNA levels for MnSOD, catalase, the catalytic subunit of gamma-glutamylcysteine ligase, GR, GST-A1, GST-P1, and NQO1 were observed. Pretreatment with sulforaphane (0.5, 1, and 5 muM) protected aortic smooth muscle cells from oxidative and electrophilic cytotoxicity induced by xanthine oxidase (XO)/xanthine, H(2)O(2), SIN-1-derived peroxynitrite, 4-hydroxy-2-nonenal, and acrolein. Furthermore, sulforaphane pretreatment prevented intracellular accumulation of reactive oxygen species (ROS) after exposure of the cells to XO/xanthine, H(2)O(2), or SIN-1. Taken together, this study demonstrates that in the aortic smooth muscle cells sulforaphane at physiologically relevant concentrations potently induces a series of total cellular as well as mitochondrial antioxidants and phase 2 enzymes, which is accompanied by dramatically increased resistance of these vascular cells to oxidative and electrophilic stress. 相似文献
106.
The ability to stably introduce genes into the germline of animals provides a powerful means to address the genetic basis
of physiology. Introduction of genes to generate transgenic animals has facilitated the development of complex genetic models
of disease, as well as the in vivo study of gene function. However, one drawback of traditional transgenic technologies in
which genes are microinjected into early-stage embryos is that there is little control over where and in how many copies genes
are introduced into the genome. The development of animal transgenic technologies, which take advantage of homologous recombination
mechanisms and the manipulation of embryonic stem (ES) cells, allows investigators to target and alter specific loci. In mouse
transgenic systems, a plethora of sophisticated gene-targeting strategies now permit investigators to manipulate the genome
in ways that essentially allow one to introduce virtually any desired change into the genome. Fur-thermore, when coupled with
systems that allow for conditional gene expression, these gene-targeting strategies allow both temporal and tissue specific
control of alterations to the genome. In the present review we briefly discuss some of the more recent gene-targeting strategies
that have been developed to address the limitations of traditional animal transgenesis. 相似文献
107.
OBJECTIVE: Methotrexate (MTX) is an important drug for treatment of rheumatoid arthritis; however, there is variation in the clinical response. MTX inhibits T cell cytokine production, with significant interindividual variability in the dose required. We investigated if the variability in clinical response was related to variability in the in vitro assay. METHODS:Patients with disease modifying antirheumatic drug-naive, active RA [1982 American College of Rheumatology (ACR) criteria] seen from September 2005 through January 2006 were enrolled. MTX was started at 10 mg/week and increased monthly by 2.5 mg/week. Baseline whole-blood cultures were set up with anti-CD3, anti-CD28, and increasing doses of MTX. Supernatants were harvested at 96 hours and tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), and interleukin 10 (IL-10) concentrations were estimated by ELISA. The dose of MTX (ID50) required for 50% suppression of production of cytokines and the change in Disease Activity Score-28 (DeltaDAS) at 4 months were noted. RESULTS: T cell stimulation resulted in significant increase in cytokine release, and addition of MTX led to a dose-dependent suppression of all 3 cytokines. There was significant negative correlation of DeltaDAS with ID50 values for TNF-alpha (R = -0.62, p < 0.01) and IFN-gamma (R = -0.43, p = 0.04). At 4 months, EULAR moderate and ACR 20% responses were achieved by 13 and 16 patients, respectively. EULAR moderate response could be predicted using ROC curves for TNF-alpha (sensitivity 93%, specificity 86%) and IFN-gamma (60% specificity, 71% sensitivity). ACR response was correctly predicted in 14 of 16 ACR 20% responders and in all ACR 50% and ACR 70% responders. CONCLUSION: An in vitro TNF-alpha suppression assay may help predict clinical response to MTX in RA. 相似文献
108.
109.
Purpose of Review
Monogenic forms of diabetes have specific treatments that differ from the standard care provided for type 1 and type 2 diabetes, making the appropriate diagnosis essential. In this review, we discuss current clinical challenges that remain, including improving case-finding strategies, particularly those that have transethnic applicability, and understanding the interpretation of genetic variants as pathogenic, with clinically meaningful impacts.Recent Findings
Biomarker approaches to the stratification for genetic testing now appear to be most effective in identifying cases of monogenic diabetes, and use of genetic risk scores may also prove useful. However, applicability in all ethnic groups is lacking. Challenges remain in the classification of genes as diabetes-causing and the interpretation of genetic variants at the clinical interface.Summary
Since the discovery that genetic defects can cause neonatal or young-onset diabetes, multiple causal genes have been identified and there have been many advances in strategies to detect genetic forms of diabetes and their treatments. Approaches learnt from monogenic diabetes are now being translated to polygenic diabetes.110.