全文获取类型
收费全文 | 639篇 |
免费 | 35篇 |
国内免费 | 11篇 |
专业分类
耳鼻咽喉 | 2篇 |
儿科学 | 29篇 |
妇产科学 | 5篇 |
基础医学 | 66篇 |
口腔科学 | 2篇 |
临床医学 | 57篇 |
内科学 | 160篇 |
皮肤病学 | 33篇 |
神经病学 | 26篇 |
特种医学 | 133篇 |
外科学 | 59篇 |
综合类 | 30篇 |
预防医学 | 23篇 |
眼科学 | 4篇 |
药学 | 26篇 |
中国医学 | 12篇 |
肿瘤学 | 18篇 |
出版年
2023年 | 1篇 |
2022年 | 4篇 |
2021年 | 4篇 |
2020年 | 12篇 |
2019年 | 9篇 |
2018年 | 9篇 |
2017年 | 4篇 |
2016年 | 9篇 |
2015年 | 10篇 |
2014年 | 14篇 |
2013年 | 32篇 |
2012年 | 28篇 |
2011年 | 23篇 |
2010年 | 18篇 |
2009年 | 23篇 |
2008年 | 33篇 |
2007年 | 28篇 |
2006年 | 18篇 |
2005年 | 14篇 |
2004年 | 13篇 |
2003年 | 20篇 |
2002年 | 10篇 |
2001年 | 16篇 |
2000年 | 17篇 |
1999年 | 9篇 |
1998年 | 41篇 |
1997年 | 34篇 |
1996年 | 18篇 |
1995年 | 16篇 |
1994年 | 16篇 |
1993年 | 19篇 |
1992年 | 6篇 |
1991年 | 6篇 |
1990年 | 10篇 |
1989年 | 16篇 |
1988年 | 16篇 |
1987年 | 15篇 |
1986年 | 14篇 |
1985年 | 17篇 |
1984年 | 6篇 |
1983年 | 7篇 |
1982年 | 10篇 |
1981年 | 7篇 |
1980年 | 9篇 |
1978年 | 10篇 |
1977年 | 7篇 |
1976年 | 4篇 |
1975年 | 3篇 |
排序方式: 共有685条查询结果,搜索用时 21 毫秒
111.
Cristina El Haj Oscar Murillo Alba Ribera Mireia Vivas Dolors Garcia-Somoza Fe Tubau Javier Cabo Javier Ariza 《Antimicrobial agents and chemotherapy》2014,58(9):5576-5580
We compared the efficacies of daptomycin (doses equivalent to 8 to 10 mg/kg of body weight/day in humans) and cloxacillin alone with those of cloxacillin-rifampin and cloxacillin-daptomycin combinations, using a tissue cage methicillin-susceptible Staphylococcus aureus (MSSA) infection model. Monotherapies were less effective than combinations (P < 0.05), and daptomycin resistance emerged. Cloxacillin-daptomycin proved as effective as cloxacillin-rifampin and prevented the appearance of resistance; this combination may be an alternative anti-MSSA therapy, which may offer greater benefits in the early treatment of prosthetic joint infections (PJI). 相似文献
112.
E. V. Simpson R. E. Ideker C. Cabo S. Yabe X. Zhou S. B. Melnick W. M. Smith 《Medical & biological engineering & computing》1993,31(2):118-128
The identification of local activation events in bipolar cardiac electrograms, the first step of isochronal map construction,
is a time-consuming and difficult process. Owing to the variability among bipolar activation complexes and the lack of practical
knowledge concerning the relationship of the bipolar waveform to action potential characteristics, a set of empirical rules
to guide the assignment of local activation times have been adopted. A computer program, called AP, has been designed, which
implements these rules in the form of a syntactic analyser. Canine epicardial recordings were used to evaluate AP by comparing
local activation times, assigned by AP, with times assigned independently by three investigators. The Hermes-Cox model for
detector evaluation and a bootstrap statistical method were used in conjunction with ROC analysis to evaluate the ability
of AP to detect events. Analysis of discrepancies among investigator-assigned times showed that the reliabilities of AP event
detection and AP-assigned times were comparable to those of the investigators. The methods used in system design and evaluation
are applicable to a broad range of problems in the detection and localisation of waveform components. 相似文献
113.
The Effects of Aging and Sex Steroid Deficiency on the Murine Skeleton Are Independent and Mechanistically Distinct
下载免费PDF全文
![点击此处可从《Journal of bone and mineral research》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Ha‐Neui Kim Li Han Christine Rutlen Kelly Allison Jeff D Thostenson Rafael de Cabo Robert L Jilka Charles O'Brien Maria Almeida Stavros C Manolagas 《Journal of bone and mineral research》2017,32(3):560-574
Old age and sex steroid deficiency are the two most critical factors for the development of osteoporosis. It remains unknown, however, whether the molecular culprits of the two conditions are similar or distinct. We show herein that at 19.5 months of age—a time by which the age‐dependent decline of cortical and cancellous bone mass and cortical porosity were fully manifested in C57BL/6J mice—these animals remained functionally estrogen sufficient. Transgenic mice with conditional expression of mitochondria‐targeted catalase—a potent H2O2 inactivating enzyme—in cells of the myeloid lineage (mitoCAT;LysM‐Cre mice) were protected from the loss of cortical, but not cancellous, bone caused by gonadectomy in either sex. Consistent with these findings, in vitro studies with ERα‐deficient Prx1+ cells and gonadectomized young adult mice showed that in both sexes decreased ERα signaling in Prx1+ cells leads to an increase in SDF1, a.k.a. CXCL12, an osteoclastogenic cytokine whose effects were abrogated in macrophages from mitoCAT;LysM‐Cre mice. In contrast to sex steroid deficiency, the adverse effects of aging on either cortical or cancellous bone were unaffected in mitoCAT;LysM‐Cre mice. On the other hand, attenuation of H2O2 generation in cells of the mesenchymal lineage targeted by Prx1‐Cre partially prevented the loss of cortical bone caused by old age. Our results suggest the effects of sex steroid deficiency and aging on the murine skeleton are independent and result from distinct mechanisms. In the former, the prevailing mechanism of the cortical bone loss in both sexes is increased osteoclastogenesis caused by estrogen deficiency; this is likely driven, at least in part, by mesenchymal/stromal cell–derived SDF1. Decreased osteoblastogenesis, owing in part to increased H2O2, combined with increased osteoclastogenesis caused by aging mechanisms independent of estrogen deficiency, are the prevailing mechanisms of the loss of cortical bone with old age. © 2016 American Society for Bone and Mineral Research. 相似文献
114.
Pearson KJ Lewis KN Price NL Chang JW Perez E Cascajo MV Tamashiro KL Poosala S Csiszar A Ungvari Z Kensler TW Yamamoto M Egan JM Longo DL Ingram DK Navas P de Cabo R 《Proceedings of the National Academy of Sciences of the United States of America》2008,105(7):2325-2330
Caloric restriction (CR) is the most potent intervention known to both protect against carcinogenesis and extend lifespan in laboratory animals. A variety of anticarcinogens and CR mimetics induce and activate the NF-E2-related factor 2 (Nrf2) pathway. Nrf2, in turn, induces a number of antioxidative and carcinogen-detoxifying enzymes. Thus, Nrf2 offers a promising target for anticarcinogenesis and antiaging interventions. We used Nrf2-disrupted (KO) mice to examine its role on the biological effects of CR. Here, we show that Nrf2 is responsible for most of the anticarcinogenic effects of CR, but is dispensable for increased insulin sensitivity and lifespan extension. Nrf2-deficient mice developed tumors more readily in response to carcinogen exposure than did WT mice, and CR was ineffective in suppressing tumors in the KO mice. However, CR extended lifespan and increased insulin sensitivity similarly in KO and WT mice. These findings identify a molecular pathway that dissociates the prolongevity and anticarcinogenic effects of CR. 相似文献
115.
García de Aguinaga ML Posada de la Paz M Estirado de Cabo E Plaza Cano Mdel M Alvarez CS Saro BB Abaitua Borda I Sánchez RG Barbado Hernández FJ 《European Journal of Internal Medicine》2008,19(1):32-39
BACKGROUND: The objective of this study was to compare current prevalence of major cardiovascular risk factors (CRF) between a cohort of patients affected by the toxic oil syndrome (TOS) epidemic, which occurred in Spain in 1981, and the unaffected Spanish population. METHODS: This was a case-referent study covering 1276 TOS cases and a referent population of 2843 (aged 35-65 years) using data collected from 1996 to 2003. Study variables were high blood pressure, hyperglycemia, dyslipemia, obesity, and metabolic syndrome. Smoking habit, alcohol intake, family and personal history of ischemic heart disease, as well as a personal history of cerebrovascular disease were also assessed in TOS patients. RESULTS: Compared to the general population, TOS patients registered a threefold rise in prevalence of diabetes, a 2.57-fold increase in hypertension, a 1.38-fold increase in total hypercholesterolemia, a 1.20-fold increase in hyper-LDL-cholesterolemia, and a high prevalence of metabolic syndrome (35% versus 25%). Nevertheless, the prevalence of hypo-HDL-cholesterolemia was significantly lower in those affected by TOS. No differences were found for other CRFs. CONCLUSION: Compared to the general population, cases display a much higher prevalence of all major CRFs. However, an increase in HDL-cholesterol protective factor is in evidence for the first time. 相似文献
116.
117.
Daniel Álvarez Cabo Antonio Alemany José Manuel Martínez Sesmero Santiago Moreno Guillén 《Enfermedades infecciosas y microbiología clínica》2018
This chapter reviews the current model of HIV patient care and its economic impact. There are clinical and geographical differences in the care HIV patients receive and a need to develop new models of comprehen-sive HIV care has been identified.HIV infection in Spain is an important and expensive public health problem. The main costs are due to an-tiretroviral therapy, indirect costs and the cost of admission, consultation and diagnostic testing. A strong correlation between severity and cost has been identified.Patients diagnosed late have a poorer clinical course, increased mortality and require more medical and therapeutic resources.Early detection of the disease significantly improves the clinical outcomes of patients.The increased number of patients receiving treatment and their progressive ageing will increase costs of HIV healthcare in the coming years. 相似文献
118.
119.
Long JM Lee GD Kelley-Bell B Spangler EL Perez EJ Longo DL de Cabo R Zou S Rapp PR 《Pharmacology, biochemistry, and behavior》2011,100(1):205-211
Some patients experience enduring cognitive impairment after cancer treatment, a condition termed “chemofog”. Animal models allow assessment of chemotherapy effects on learning and memory per se, independent of changes due to cancer itself or associated health consequences such as depression. The present study examined the long-term learning and memory effects of a chemotherapy cocktail used widely in the treatment of breast cancer, consisting of 5-fluorouracil (5FU) and cyclophosphamide (CYP). Eighty 5-month old male F344 rats received contextual and cued fear conditioning before treatment with saline, or a low or high dose drug cocktail (50 mg/kg CYP and 75 mg/kg 5FU, or 75 mg/kg CYP and 120 mg/kg 5FU, i.p., respectively) every 30 days for 2 months. After a 2-month, no-drug recovery, both long-term retention and new task acquisition in the water maze and 14-unit T-maze were assessed. Neither dose of the CYP/5FU cocktail impaired retrograde fear memory despite marked toxicity documented by enduring weight loss and 50% mortality at the higher dose. Acquisition in the water maze and Stone maze was also normal relative to controls in rats treated with CYP/5FU. The results contribute to a growing literature suggesting that learning and memory mediated by the hippocampus can be relatively resistant to chemotherapy. Future investigation may need to focus on assessments of processing speed, executive function and attention, and the possible interactive contribution of cancer itself and aging to the post-treatment development of cognitive impairment. 相似文献
120.
INTRODUCTION: Reversible acetylation is a key post-translational modification of target proteins. Sirtuin deacetylases represent the homolog of the yeast silent information regulator (SIR2). Although seven sirtuins have been found in mammals, all sirtuin activators described to date act through SIRT1. AREAS COVERED: Areas covered in this paper include a review of the patent literature associated with SIRT1 activators, with a focus on therapeutic applications, primarily related to the use of pharmaceuticals and nutraceuticals containing resveratrol (RSV), and the development of second-generation activators unrelated to RSV. Also discussed is the current controversy over whether or not these molecules are actual SIRT1 activators. EXPERT OPINION: Developing effective strategies to protect against diet-induced metabolic imbalance is necessary to fight against current obesity rates. The hypothalamus is a candidate for developing drugs that suppress SIRT1 degradation, as a strategy for treating metabolic syndrome. Deciphering the basic mechanism of activators is essential to develop effective strategies to alter sirtuin activity. This is true regardless of the apparent controversy of whether in vitro activation of SIRT1 is direct or not, depending on the experimental design, and whether sirtuins may play a major role in longevity. The numerous studies on their positive effects against age-related diseases, obesity and other metabolic disorders are still valid, promising to positively influence the development of treatments to improve human health. 相似文献