全文获取类型
收费全文 | 96614篇 |
免费 | 6915篇 |
国内免费 | 508篇 |
专业分类
耳鼻咽喉 | 1209篇 |
儿科学 | 2312篇 |
妇产科学 | 1384篇 |
基础医学 | 12460篇 |
口腔科学 | 2309篇 |
临床医学 | 9539篇 |
内科学 | 21335篇 |
皮肤病学 | 1517篇 |
神经病学 | 9230篇 |
特种医学 | 3956篇 |
外国民族医学 | 1篇 |
外科学 | 16063篇 |
综合类 | 802篇 |
一般理论 | 194篇 |
预防医学 | 6559篇 |
眼科学 | 1834篇 |
药学 | 5903篇 |
中国医学 | 140篇 |
肿瘤学 | 7290篇 |
出版年
2023年 | 865篇 |
2022年 | 1498篇 |
2021年 | 3285篇 |
2020年 | 1821篇 |
2019年 | 2823篇 |
2018年 | 3319篇 |
2017年 | 2350篇 |
2016年 | 2542篇 |
2015年 | 2854篇 |
2014年 | 3942篇 |
2013年 | 5048篇 |
2012年 | 7640篇 |
2011年 | 7741篇 |
2010年 | 4269篇 |
2009年 | 3703篇 |
2008年 | 6370篇 |
2007年 | 6143篇 |
2006年 | 5953篇 |
2005年 | 5867篇 |
2004年 | 5289篇 |
2003年 | 4849篇 |
2002年 | 4355篇 |
2001年 | 617篇 |
2000年 | 489篇 |
1999年 | 692篇 |
1998年 | 894篇 |
1997年 | 713篇 |
1996年 | 577篇 |
1995年 | 567篇 |
1994年 | 453篇 |
1993年 | 460篇 |
1992年 | 368篇 |
1991年 | 325篇 |
1990年 | 298篇 |
1989年 | 289篇 |
1988年 | 294篇 |
1987年 | 267篇 |
1986年 | 293篇 |
1985年 | 293篇 |
1984年 | 360篇 |
1983年 | 323篇 |
1982年 | 343篇 |
1981年 | 341篇 |
1980年 | 264篇 |
1979年 | 155篇 |
1978年 | 193篇 |
1977年 | 183篇 |
1976年 | 130篇 |
1975年 | 135篇 |
1974年 | 132篇 |
排序方式: 共有10000条查询结果,搜索用时 203 毫秒
161.
162.
The use of 19F spectroscopy and diffusion-weighted MRI to evaluate differences in gene-dependent enzyme prodrug therapies. 总被引:4,自引:0,他引:4
Daniel A Hamstra Kuei C Lee Joseph M Tychewicz Victor D Schepkin Bradford A Moffat Mark Chen Kenneth J Dornfeld Theodore S Lawrence Thomas L Chenevert Brian D Ross Juri T Gelovani Alnawaz Rehemtulla 《Molecular therapy》2004,10(5):916-928
To evaluate noninvasive measures of gene expression and tumor response in a gene-dependent enzyme prodrug therapy (GDEPT), a bifunctional fusion gene between Saccharomyces cerevisiae cytosine deaminase (CD) and Haemophilus influenzae uracil phosphoribosyltransferase (UPRT) was constructed. CD deaminates 5-fluorocytosine (5FC) to 5-fluorouracil (5FU), and UPRT subsequently converts 5FU to fluorouridine monophosphate, and both of these reactions can be monitored noninvasively in vitro and in vivo using 19F magnetic resonance spectroscopy (MRS). Following transient transfection the CD-UPRT fusion protein exhibited both UPRT and CD enzymatic activities as documented by 19F MRS. In addition, an increase in CD activity and thermal stability was witnessed for the fusion protein compared to native CD. Stable expression of CD-UPRT in 9L glioma cells increased both 5FC and 5FU sensitivity in vitro compared to CD-expressing and wild-type 9L cells. Noninvasive 19F MRS of both CD and UPRT gene function in vivo demonstrated that in animals bearing CD-expressing tumors there was limited conversion of 5FC to 5FU with no measurable accumulation of cytotoxic fluorinated nucleotides (F-nucs). In contrast, CD-UPRT-expressing tumors had increased CD gene activity with a threefold higher intratumoral accumulation of 5FU and significant generation of F-nucs. Finally, CD-UPRT yielded increased efficacy in an orthotopic animal model of high-grade glioma. More importantly, early changes in cellular water mobility, which are felt to reflect cellular death, as measured by diffusion-weighted MRI, were predictive of both durable response and increased animal survival. These results demonstrate the increased efficacy of the CD-UPRT GDEPT compared to CD alone both biochemically and in a preclinical model and validate both 19F MRS and diffusion-weighted MRI as tools to assess gene function and therapeutic efficacy. 相似文献
163.
Sanjeev Kakar Thomas A Einhorn Siddharth Vora Lincoln J Miara Gregory Hon Nathan A Wigner Daniel Toben Kimberly A Jacobsen Maisa O Al-Sebaei Michael Song Philip C Trackman Elise F Morgan Louis C Gerstenfeld George L Barnes 《Journal of bone and mineral research》2007,22(12):1903-1912
Studies have shown that systemic PTH treatment enhanced the rate of bone repair in rodent models. However, the mechanisms through which PTH affects bone repair have not been elucidated. In these studies we show that PTH primarily enhanced the earliest stages of endochondral bone repair by increasing chondrocyte recruitment and rate of differentiation. In coordination with these cellular events, we observed an increased level of canonical Wnt-signaling in PTH-treated bones at multiple time-points across the time-course of fracture repair, supporting the conclusion that PTH responses are at least in part mediated through Wnt signaling. INTRODUCTION: Since FDA approval of PTH [PTH(1-34); Forteo] as a treatment for osteoporosis, there has been interest in its use in other musculoskeletal conditions. Fracture repair is one area in which PTH may have a significant clinical impact. Multiple animal studies have shown that systemic PTH treatment of healing fractures increased both callus volume and return of mechanical competence in models of fracture healing. Whereas the potential for PTH has been established, the mechanism(s) by which PTH produces these effects remain elusive. MATERIALS AND METHODS: Closed femoral fractures were generated in 8-wk-old male C57Bl/6 mice followed by daily systemic injections of either saline (control) or 30 microg/kg PTH(1-34) for 14 days after fracture. Bones were harvested at days 2, 3, 5, 7, 10, 14, 21, and 28 after fracture and analyzed at the tissue level by radiography and histomorphometry and at the molecular and biochemical levels level by RNase protection assay (RPA), real-time PCR, and Western blot analysis. RESULTS: Quantitative muCT analysis showed that PTH treatment induced a larger callus cross-sectional area, length, and total volume compared with controls. Molecular analysis of the expression of extracellular matrix genes associated with chondrogenesis and osteogenesis showed that PTH treated fractures displayed a 3-fold greater increase in chondrogenesis relative to osteogenesis over the course of the repair process. In addition, chondrocyte hypertrophy occurred earlier in the PTH-treated callus tissues. Analysis of the expression of potential mediators of PTH actions showed that PTH treatment significantly induced the expression of Wnts 4, 5a, 5b, and 10b and increased levels of unphosphorylated, nuclear localized beta-catenin protein, a central feature of canonical Wnt signaling. CONCLUSIONS: These results showed that the PTH-mediated enhancement of fracture repair is primarily associated with an amplification of chondrocyte recruitment and maturation in the early fracture callus. Associated with these cellular effects, we observed an increase in canonical Wnt signaling supporting the conclusion that PTH effects on bone repair are mediated at least in part through the activation of Wnt-signaling pathways. 相似文献
164.
Rachel M Massey Oliver J Warren Michal Szczeklik Sophie Wallace Daniel R Leff John Kokotsakis Ara Darzi Thanos Athanasiou 《Journal of cardiothoracic surgery》2007,2(1):26-9
The use of a skeletonized internal thoracic artery in coronary artery bypass graft surgery has been shown to confer certain
advantages over a traditional pedicled technique, particularly in certain patient groups. Recent reports indicate that radial
and gastroepiploic arteries can also be harvested using a skeletonized technique. The aim of this study is to systematically
review the available evidence regarding the use of skeletonized radial and gastroepiploic arteries within coronary artery
bypass surgery, focusing specifically on it's effect on conduit length and flow, levels of endothelial damage, graft patency
and clinical outcome. Four electronic databases were systematically searched for studies reporting the utilisation of the
skeletonization technique within coronary revascularisation surgery in humans. Reference lists of all identified studies were
checked for any missing publications. There appears to be some evidence that skeletonization may improve angiographic patency,
when compared with pedicled vessels in the short to mid-term. We have found no suggestion of increased complication rates
or increased operating time. Skeletonization may increase the length of the conduit, and the number of sequential graft sites,
but no clear clinical benefits are apparent. Our study suggests that there is not enough high quality or consistent evidence
to currently advocate the application of this technique to radial or gastroepiploic conduits ahead of a traditional pedicled
technique. 相似文献
165.
Mohamad H Yamani Daniel J Cook E Murat Tuzcu Philip Paul Norman B Ratliff Yang Yu Robert Hobbs Gustavo Rincon Corinne Bott-Silverman Nicholas Smedira James B Young Randall C Starling 《The Journal of heart and lung transplantation》2005,24(8):1014-1018
BACKGROUND: Recipients of hearts from donors with spontaneous intracerebral hemorrhage (ICH) are at increased risk of allograft vasculopathy compared with trauma donors. We have recently shown that the vitronectin receptor (integrin alpha(V)beta3) is upregulated in transplant vasculopathy. We hypothesized that donor ICH is associated with systemic activation of alpha(V)beta3 in the donor before transplantation. METHODS: We evaluated mRNA expressions of alpha(V)beta3 (TaqMan PCR) in endomyocardial biopsy samples at 1-week post-transplant in 20 recipients from ICH donors and 20 recipients from trauma donors. To investigate whether systemic activation of alpha(V)beta3 was present in the donor before transplantation, alpha(V)beta3 expression was also evaluated in the corresponding donor spleen lymphocytes. All patients underwent serial coronary intravascular ultrasound to evaluate for coronary vasculopathy. The baseline characteristics were similar except for increased donor age in the ICH Group. RESULTS: The ICH Group showed significant increased mRNA expression of alpha(V)beta3 in the heart biopsy samples (3.8-fold, p = 0.012) and in the corresponding donor spleen lymphocytes (3.5-fold, p = 0.014) compared with the Trauma Group. At 1 year, the ICH Group also showed increased progression of coronary vasculopathy. Multivariate regression analysis found that donor lymphocytic alpha(V)beta3 mRNA expression was independently associated with increased risk of vasculopathy (odds ratio, 1.9; 95% CI, 1.21-3.98, p = 0.03). CONCLUSIONS: Our report demonstrates the presence of systemic activation of alpha(V)beta3 in donors with spontaneous intracerebral hemorrhage and its association with the subsequent development of allograft vasculopathy in the recipient. 相似文献
166.
Kulbir S. Walia MD ; Daniel E. Muser MD ; Shariq S. Raza MD ; Tricia Griech MSPT ; Yasin N. Khan MD 《Pain practice》2004,4(4):303-306
Abstract: We present a case of a 13-year-old boy who developed signs and symptoms of neuropathic pain/early Complex Regional Pain Syndrome (CRPS) Type I, formerly known as Reflex Sympathetic Dystrophy (RSD), after spraining his ankle while wrestling. Aggressive pain control, using medications and sympatholytic blocks, with physical therapy and rehabilitation, led to the resolution of his painful condition. This prevented the disease from possibly progressing to a full-blown case of CRPS I (RSD) that is very challenging to treat. 相似文献
167.
Sean J. Barnett M.S. M.D. Christopher Stanley B.S. Melanie Hanlon R.N. C.N.P. Robert Acton M.D. Daniel A. Saltzman M.D. Ph.D. Sayeed Ikramuddin M.D. Henry Buchwald M.D. Ph.D. 《Surgery for obesity and related diseases》2005,1(4):1609-398
PURPOSE: Obesity has become a health-care crisis in the United States. Adolescent obesity is now one of the most common childhood disorders, with 4.7 million American adolescents having a body mass index (BMI) greater than the 95th percentile. Most patients do not respond to diet modification or exercise programs and attention is now turning toward surgery as a source of weight loss in adolescents. Few studies have looked at the overall morbidity and mortality of weight loss surgery in this patient population. METHODS: This is a retrospective study of medical charts of 15 bariatric surgical procedures performed on 14 adolescents without known genetic syndromes associated with severe childhood obesity from 1971 to 2001 at the University of Minnesota. Procedures performed on these patients included vertical banded gastroplasty (n = 7), Roux-en-Y gastric bypass (n = 5), and jejunoileal bypass (n = 3). Jejunoileal bypass procedures were performed from 1971 to 1977, after which time this procedure was abandoned. Patient age ranged from 13 to 17 years (mean, 15.7 years). Mean follow-up time was 6 years, with 9 patients available for long-term follow-up. RESULTS: All procedures were performed using an open technique by 1 surgeon. There were no perioperative deaths; complications included 1 case of wound infection, 2 episodes of dumping syndrome that resolved without revision, 1 episode of hypoglycemia, and 1 case of short-term electrolyte imbalance in a patient who underwent jejunoileal bypass. The average BMI dropped from 58.5 +/- 13.7 to 32.1 +/- 9.7 kg/m(2) (P < .01)--a 45% reduction. CONCLUSIONS: Surgery for morbid obesity is safe and results in significant weight loss in adolescents who fail medical therapy. 相似文献
168.
Carlos Estrela Cyntia Rodrigues de Araújo Estrela Augusto César Braz Hollanda Daniel de Almeida Decurcio Jesus Djalma Pécora 《Journal of applied oral science : revista FOB》2006,14(1):33-37
The purpose of this research was to verify the influence of Iodoform on antimicrobial potential of calcium hydroxide. S. aureus, E. faecalis, P. aeruginosa, B. subtilis, C. albicans were the biological indicators. The substances tested were: calcium hydroxide + saline; calcium hydroxide + Iodoform + saline; Iodoform + saline. For the agar diffusion test, 18 Petri plates with 20 ml of BHI agar were inoculated with the microbial suspensions. Fifty-four cavities were made and filled with the substances tested. The diameters of microbial inhibition were then measured. In direct exposure test, 162 #50 sterile absorbent paper points were immersed in the experimental suspensions for 5 min, and covered with the pastes. At intervals of 24, 48 and 72 hours, the paper points were immersed in 10 ml of Letheen Broth, followed by incubation at 37°°C for 48h. Microbial growth was evaluated by turbidity of the culture medium. A 0.1 ml inoculum obtained from the Letheen Broth was transferred to 7 ml of BHI, and incubated at 37°°C for 48h. Bacterial growth was again evaluated by turbidity of the culture medium. The calcium hydroxide associated with the saline or the iodoform plus saline showed antimicrobial effectiveness in both experimental methods. The iodoform paste presented antimicrobial ineffectiveness for the agar diffusion test on all biological microorganisms and for the direct exposure test on B. subtilis and on the mixture. 相似文献
169.
170.