全文获取类型
收费全文 | 51992篇 |
免费 | 3488篇 |
国内免费 | 215篇 |
专业分类
耳鼻咽喉 | 770篇 |
儿科学 | 1254篇 |
妇产科学 | 709篇 |
基础医学 | 6713篇 |
口腔科学 | 938篇 |
临床医学 | 5119篇 |
内科学 | 11050篇 |
皮肤病学 | 413篇 |
神经病学 | 5637篇 |
特种医学 | 2045篇 |
外国民族医学 | 1篇 |
外科学 | 7855篇 |
综合类 | 526篇 |
一般理论 | 86篇 |
预防医学 | 4182篇 |
眼科学 | 1127篇 |
药学 | 3671篇 |
中国医学 | 69篇 |
肿瘤学 | 3530篇 |
出版年
2023年 | 245篇 |
2022年 | 436篇 |
2021年 | 1060篇 |
2020年 | 603篇 |
2019年 | 1015篇 |
2018年 | 1256篇 |
2017年 | 906篇 |
2016年 | 984篇 |
2015年 | 1140篇 |
2014年 | 1687篇 |
2013年 | 2303篇 |
2012年 | 3611篇 |
2011年 | 3751篇 |
2010年 | 2094篇 |
2009年 | 1736篇 |
2008年 | 3393篇 |
2007年 | 3603篇 |
2006年 | 3482篇 |
2005年 | 3525篇 |
2004年 | 3255篇 |
2003年 | 3066篇 |
2002年 | 3000篇 |
2001年 | 535篇 |
2000年 | 445篇 |
1999年 | 556篇 |
1998年 | 625篇 |
1997年 | 541篇 |
1996年 | 443篇 |
1995年 | 475篇 |
1994年 | 349篇 |
1993年 | 371篇 |
1992年 | 343篇 |
1991年 | 328篇 |
1990年 | 308篇 |
1989年 | 279篇 |
1988年 | 240篇 |
1987年 | 256篇 |
1986年 | 237篇 |
1985年 | 264篇 |
1984年 | 293篇 |
1983年 | 254篇 |
1982年 | 311篇 |
1981年 | 313篇 |
1980年 | 257篇 |
1979年 | 168篇 |
1978年 | 172篇 |
1977年 | 179篇 |
1976年 | 145篇 |
1975年 | 97篇 |
1974年 | 85篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
101.
Dorit Naot Usha Bava Brya Matthews Karen E Callon Gregory D Gamble Michael Black Sarah Song Rocco P Pitto Tim Cundy Jill Cornish Ian R Reid 《Journal of bone and mineral research》2007,22(2):298-309
Paget's disease is a focal condition of bone. To study changes in cells within pagetic lesions, we cultured osteoblasts and stromal cells from 22 patients and compared gene expression in these cells to cells from healthy bone. We identified several differentially regulated genes, and we suggest that these changes could lead to the formation of the lesions. INTRODUCTION: Paget's disease is a focal condition of bone of unknown cause. Although it is regarded as primarily an osteoclast disorder, the tight coupling of the activity of osteoclasts and osteoblasts suggests that the osteoblast could play a key role in its pathogenesis. The aim of the study was to identify possible changes in pagetic osteoblasts and stromal cells that might contribute to the development of pagetic lesions. MATERIALS AND METHODS: Candidate genes were identified based on known bone cell regulators, supplemented with microarray analysis. Gene expression was determined by real-time PCR in primary cultures of osteoblasts and bone marrow stromal cells from pagetic patients and control subjects. Concentrations of secreted proteins were determined by ELISA. RESULTS: Dickkopf1 mRNA and protein levels were increased in both pagetic osteoblast and stromal cell cultures, and interleukin (IL)-1 and IL-6 were overexpressed in pagetic osteoblasts. These changes parallel recent findings in myeloma bone disease, which shares some clinical similarities with Paget's disease. Alkaline phosphatase was overexpressed, and bone sialoprotein and osteocalcin were underexpressed in pagetic osteoblasts, consistent with their circulating levels in pagetic patients. It is hypothesized that overexpression of Dickkopf1, IL-1, and IL-6 would result in stimulation of osteoclast proliferation and inhibition of osteoblast growth, leading to the development of the characteristic lytic bone lesions. By stimulating osteoblast differentiation, Dickkopf1 and IL-6 may also promote mineralization, leading to the conversion of lytic lesions to sclerotic. CONCLUSIONS: These findings suggest that dysregulated gene expression in pagetic osteoblasts could cause the changes in bone cell number and function characteristic of Paget's disease. 相似文献
102.
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
103.
Richard O. Wein MD Gregory S. Weinstein MD 《Operative Techniques in Otolaryngology》2003,14(2):129-149
The elective surgical treatment of the neck for advanced T-stage laryngeal presentations of squamous cell carcinoma is typically the anterolateral neck dissection. Modifications of the anterior-based technique that include the use of digastric and hypoglossal tunnels to establish reliable landmarks result in a reproducible technique. The complex anatomic relationships of the anterior and superior part of the neck dissection are exposed and protected early in the technique, making this approach ideal for use in an academic setting. 相似文献
104.
CPT Tony Pierson Jeffrey A. Niezgoda MD LT Sarah Learmonth CPT Dennis Blunt LTC Kevin McNabb 《Wound repair and regeneration》2005,13(2):1-2
Abstract Brooke Army Medical Center isolated 25 highly antibiotic‐resistant Acinetobacter ssp . (primarily A. baumannii ) from wounded soldiers returning from Iraq. Concern about effective treatment of these organisms led our institution to begin investigating low‐frequency ultrasound (LFU) as a method of increasing the effectiveness of antibiotics on A.baumannii in wound management. Studies have suggested that LFU applied in conjunction with antibiotics may increase their overall effectiveness. We hypothesize that combining antibiotics with LFU may be an effective method of wound management and that this combination may be synergistic in its overall effect. In this initial work, we wanted to determine if sonocation would have an effect on our organism of interest, A. baumannii . We selected several organisms, both gram positive and gram negative, that have been shown to be killed by sonocation ( E. coli, S. aureus , and S. pyogenes ) and added three highly resistant A. baumannii isolates. Bacterial death was measured by both colony counts after 24 hours of growth and acridine orange staining using a standard protocol.
Colony counts were significantly reduced by sonocation. Furthermore, A.'baumannii colony counts were also greatly reduced by sonocation. Actual cell destruction was also visualized using acridine orange staining. Our data support the assertion that sonocation has an antibacterial effect on some bacteria, including A. baumannii . Our next step is to add antimicrobial agents and determine if their effectiveness can be increased by sonocation. 相似文献
Colony counts were significantly reduced by sonocation. Furthermore, A.'baumannii colony counts were also greatly reduced by sonocation. Actual cell destruction was also visualized using acridine orange staining. Our data support the assertion that sonocation has an antibacterial effect on some bacteria, including A. baumannii . Our next step is to add antimicrobial agents and determine if their effectiveness can be increased by sonocation. 相似文献
105.
106.
107.
Marjan Boerma Gregory R Burton Junru Wang Louis M Fink Robert E McGehee Martin Hauer-Jensen 《Blood coagulation & fibrinolysis》2006,17(3):173-180
Immortalized cell lines offer significant logistical advantages over primary cells when used for in-vitro studies. Immortalized cells may, however, exhibit important differences relative to their primary cell counterparts. In this study, microarrays were used to make a genome-wide comparison between primary human umbilical vein endothelial cells (HUVECs) and EA.hy926, an immortalized HUVEC cell line, in their baseline properties and in their response to inhibition of the mevalonate pathway with an inhibitor of hydroxy methylglutaryl-coenzyme A reductase (statin). HUVECs and EA.hy926 were incubated with control medium, atorvastatin, mevalonate, or a combination of atorvastatin and mevalonate for 24 h. Gene expression profiles were obtained in duplicates using Affymetrix Human Genome U133A 2.0 arrays (Santa Clara, California, USA). Probe-sets were selected according to the following criteria: a twofold or greater increase/decrease in atorvastatin-treated cells compared with untreated cells; a twofold or greater reversal of the effect of atorvastatin by combined treatment with atorvastatin and mevalonate; no significant change in gene expression in cells treated with mevalonate alone compared with untreated cells. Most genes that were expressed by untreated HUVECs, were also expressed by untreated EA.hy926 cells. EA.hy926 cells, however, constitutively expressed a large number of additional genes, many of which were related to cell cycle control and apoptosis. Atorvastatin induced differential expression (> or = twofold) of 103 genes in HUVECs (10 up, 93 down) and 466 genes in EA.hy926 cells (198 up, 268 down). Applying the above selection criteria, thrombomodulin and tissue plasminogen activator were up-regulated in both cell types, whereas, connective tissue growth factor, thrombospondin-1, and cysteine-rich angiogenic inducer 61 were down-regulated. In conclusion, EA.hy926 cells retain most of the characteristics of endothelial cells under baseline conditions as well as after treatment with atorvastatin. It is necessary, however, to carefully select and validate changes in genes that are the focus of studies when using EA.hy926 cells. While this cell line is highly useful in studies on some genes, including genes encoding molecules involved in regulating thrombohemorrhagic homeostasis, they appear to be less suited for studies focused on other genes, particularly those involved in the regulation of cell proliferation and apoptosis. 相似文献
108.
109.
Steven N Singh X Charlene Tang Bramah N Singh Paul Dorian Domenic J Reda Crystal L Harris Ross D Fletcher Satish C Sharma J Edwin Atwood Alan K Jacobson H Daniel Lewis Becky Lopez Dennis W Raisch Michael D Ezekowitz 《Journal of the American College of Cardiology》2006,48(4):721-730
OBJECTIVES: The purpose of this study was to determine quality of life (QOL) and exercise performance (EP) in patients with persistent atrial fibrillation (AF) converted to sinus rhythm (SR) compared with those remaining in or reverting to AF. BACKGROUND: Restoration of SR in patients with AF improving QOL and EP remains controversial. METHODS: Patients with persistent AF were randomized double-blind to amiodarone, sotalol, or placebo. Those not achieving SR at day 28 were cardioverted and classified into SR or AF groups at 8 weeks (n = 624) and 1 year (n = 556). The QOL (SF-36), symptom checklist (SCL), specific activity scale (SAS), AF severity scale (AFSS), and EP were assessed. RESULTS: Favorable changes were seen in SR patients at 8 weeks in physical functioning (p < 0.001), physical role limitations (p = 0.03), general health (p = 0.002), and vitality (p < 0.001), and at 1 year in general health (p = 0.007) and social functioning (p = 0.02). Changes in the scores for SCL severity (p = 0.01), functional capacity (p = 0.003), and AFSS symptom burden (p < 0.001) at 8 weeks and in SCL severity (p < 0.01) and AF symptom burden (p < 0.001) at 1 year showed significant improvements in SR versus AF. Symptomatic patients were more likely to have improvement. The EP in SR versus AF was greater from baseline to 8 weeks (p = 0.01) and to 1 year (p = 0.02). The EP correlated with physical functioning and functional capacity except in the AF group at 1 year. CONCLUSIONS: In patients with persistent AF, restoration and maintenance of SR was associated with improvements in QOL measures and EP. There was a strong correlation between QOL measures and EP. 相似文献
110.