全文获取类型
收费全文 | 2293篇 |
免费 | 100篇 |
国内免费 | 31篇 |
专业分类
耳鼻咽喉 | 6篇 |
儿科学 | 97篇 |
妇产科学 | 23篇 |
基础医学 | 460篇 |
口腔科学 | 91篇 |
临床医学 | 259篇 |
内科学 | 518篇 |
皮肤病学 | 112篇 |
神经病学 | 64篇 |
特种医学 | 268篇 |
外科学 | 194篇 |
综合类 | 48篇 |
预防医学 | 73篇 |
眼科学 | 25篇 |
药学 | 141篇 |
中国医学 | 1篇 |
肿瘤学 | 44篇 |
出版年
2018年 | 23篇 |
2016年 | 24篇 |
2015年 | 28篇 |
2014年 | 23篇 |
2013年 | 79篇 |
2012年 | 31篇 |
2010年 | 51篇 |
2009年 | 42篇 |
2008年 | 36篇 |
2007年 | 55篇 |
2006年 | 49篇 |
2005年 | 34篇 |
2004年 | 27篇 |
2003年 | 31篇 |
2002年 | 25篇 |
2001年 | 35篇 |
2000年 | 24篇 |
1999年 | 36篇 |
1998年 | 82篇 |
1997年 | 96篇 |
1996年 | 105篇 |
1995年 | 70篇 |
1994年 | 73篇 |
1993年 | 78篇 |
1992年 | 42篇 |
1991年 | 36篇 |
1990年 | 42篇 |
1989年 | 66篇 |
1988年 | 59篇 |
1987年 | 48篇 |
1986年 | 51篇 |
1985年 | 38篇 |
1984年 | 55篇 |
1983年 | 27篇 |
1982年 | 31篇 |
1981年 | 37篇 |
1980年 | 49篇 |
1979年 | 23篇 |
1978年 | 27篇 |
1977年 | 35篇 |
1976年 | 38篇 |
1975年 | 36篇 |
1972年 | 24篇 |
1970年 | 23篇 |
1965年 | 50篇 |
1964年 | 50篇 |
1963年 | 47篇 |
1962年 | 41篇 |
1961年 | 40篇 |
1960年 | 65篇 |
排序方式: 共有2424条查询结果,搜索用时 15 毫秒
91.
恰如其分的外周髓鞘形成取决于雪旺细胞增殖与分化进程间的平衡。丝氨酸/苏氨酸激酶(mTOR)整合多种环境因素,是细胞生长、代谢、发挥作用的中枢调节者。本文报道了一种mTOR的负性调节剂——结节性硬化复合体(TSC1),通过控制细胞增殖和髓鞘稳态,建立了雪旺细胞谱系进展和髓鞘形成的阶段依赖性程序。小鼠雪旺细胞祖细胞中TSC1的解离导致mTOR信号通路激活,继而导致雪旺细胞过量增殖,分化受阻,髓鞘形成减少。转录组分析显示,TSC1突变体中的mTOR活化使得polo样激酶(PLK)依赖性通路和细胞周期调节剂上调。弱化mTOR或者对PLK进行药理抑制部分挽救了因TSC1缺失导致的外周神经发育过程中的髓鞘形成减少。相较之下,成年小鼠成熟雪旺细胞中TSC1缺失可导致髓鞘的过度增殖和过度生长。本文的发现提示了TSC1-mTOR-PLK信号轴在控制雪旺细胞的发育过程中,从增殖到分化和髓鞘内稳态中起到的阶段特异性功能。 相似文献
92.
Bone tissue engineering in oral peri‐implant defects in preclinical in vivo research: A systematic review and meta‐analysis 下载免费PDF全文
Siddharth Shanbhag Nikolaos Pandis Kamal Mustafa Jens R. Nyengaard Andreas Stavropoulos 《Journal of tissue engineering and regenerative medicine》2018,12(1):e336-e349
The regeneration and establishment of osseointegration within oral peri‐implant bone defects remains a clinical challenge. Bone tissue engineering (BTE) is emerging as a promising alternative to autogenous and/or biomaterial‐based bone grafting. The objective of this systematic review was to answer the focused question: in animal models, do cell‐based BTE strategies enhance bone regeneration and/or implant osseointegration in experimental peri‐implant defects, compared with grafting with autogenous bone or only biomaterial scaffolds? Electronic databases were searched for controlled animal studies reporting on peri‐implant defects and implantation of mesenchymal stem cells (MSC) or other cells seeded on biomaterial scaffolds, following Preferred Reporting Items for Systematic reviews and Meta‐Analyses (PRISMA) guidelines. Random effects meta‐analyses were performed for the outcomes histomorphometric bone area fraction (BA) and bone‐to‐implant contact (BIC). Nineteen studies reporting on large animal models (dogs and sheep) were included. Experimental defects were created surgically (16 studies) or via ligature‐induced peri‐implantitis (LIPI, three studies). In general, studies presented with an unclear to high risk of bias. In most studies, MSC were used in combination with alloplastic mineral phase or polymer scaffolds; no study directly compared cell‐loaded scaffolds vs. autogenous bone. In three studies, cells were also modified by ex vivo gene transfer of osteoinductive factors. The meta‐analyses indicated statistically significant benefits in favour of: (a) cell‐loaded vs. cell‐free scaffolds [weighted mean differences (WMD) of 10.73–12.30% BA and 11.77–15.15% BIC] in canine surgical defect and LIPI models; and (b) gene‐modified vs. unmodified cells (WMD of 29.44% BA and 16.50% BIC) in canine LIPI models. Overall, heterogeneity in the meta‐analyses was high (I2 70–88%); considerable variation was observed among studies regarding the nature of cells and scaffolds used. In summary, bone regeneration and osseointegration in peri‐implant defects are enhanced by the addition of osteogenic cells to biomaterial scaffolds. Although the direction of treatment outcome is clearly in favour of BTE strategies, due to the limited magnitude of treatment effect observed, no conclusive statements regarding the clinical benefit of such procedures for oral indications can yet be made. Copyright © 2017 John Wiley & Sons, Ltd. 相似文献
93.
94.
The impact of experimental diabetes mellitus in rats on glomerular capillary number and sizes 总被引:11,自引:0,他引:11
Summary The structural counterpart of the increased glomerular filtration found in acute diabetes mellitus and experimental diabetes has been ascribed to the increased glomerular filtration surface. Using modern design-based stereological methods and light microscopy on perfusionfixed rat kidneys the average total surface area of capillaries per glomerulus in control rats was 291±42 10–3 mm2 (±SD) increasing to 383±55 10–3 mm2 in 10-day-diabetic rats. There was a further increase to 469±70 10–3 mm2 in 50-day-diabetic rats. The average total length of capillaries per glomerulus increased from 12.5±2.2 mm in the control rats to 16.9±2.4 mm in the 10-day-diabetic rats whereas the further increase to 19.4±3.0 mm in the 50-day-diabetic rats failed to reach statistical significance. The average number of topologically defined capillaries per glomerulus increased from 215±29 in the control rats to 260±45 and 316±29 in the 10-day-diabetic and 50-day-diabetic rats, respectively. The results showed just a slight increase in the mean length of a capillary from 58.1±6.2 m in the control rats to 65.6±2.6 m in the 10-day-diabetic rats after which it normalized in the 50-day-diabetic rats to 61.3±3.6 m. The geometric factor or resistance in Poiseuille's law did not differ between the three groups, neither did the diameter of the capillaries, nor the number of glomeruli. The implications of the formation of capillaries in renal glomeruli are discussed and it is concluded that glomerular capillaries in experimental diabetes grow mainly by the formation of new capillaries. 相似文献
95.
96.
Annemarie Brüel Jens R Nyengaard Carl Christian Danielsen 《Growth hormone & IGF research》2006,16(3):193-201
In cardiac hypertrophy induced by GH, the turn-over of collagen seems to be increased. Matrix metalloproteinases (MMP) are enzymes suggested to contribute to the remodelling of the extracellular matrix in the myocardium. The aim of the present experiment was to investigate how GH influenced MMP concentration, collagen concentration, and structure of the connective tissue of the LV in young rats in relation to time. Three-month-old female rats were injected with GH (5mg/kg/day) or vehicle for 5, 10, 20, 40, or 80 days. MMPs and structural changes of the connective tissue were analysed using zymography and stereology, respectively. Wet weight of the LV was increased time-dependently by GH (r = 0.89, P < 0.001). Furthermore, GH increased the MMP-2 concentration (P < 0.01, two-way ANOVA), whereas no collagenases (MMP-1, MMP-8, or MMP-13) could be demonstrated. The increase in MMP-2 was accompanied by a time-dependent decrease in the collagen concentration (r = -0.46, P < 0.05), whereas the total collagen content (r = 0.85, P < 0.01) and total number of non-myocyte nuclei (GH: r = 0.89, P < 0.001) were time-dependently increased. These results indicate that MMP-2 may be involved in the remodelling process of the extracellular matrix in GH-induced cardiac hypertrophy. 相似文献
97.
NA Hanchard DR Murdock PL Magoulas M Bainbridge D Muzny YQ Wu M Wang AL McGuire JR Lupski RA Gibbs CW Brown 《Clinical genetics》2013,83(5):457-461
The advent of whole‐exome next‐generation sequencing (WES) has been pivotal for the molecular characterization of Mendelian disease; however, the clinical applicability of WES has remained relatively unexplored. We describe our exploration of WES as a diagnostic tool in a 3½‐year old female patient with a 2‐year history of episodic muscle weakness and paroxysmal dystonia who presented following a previous extensive but unrevealing diagnostic work‐up. WES was performed on the proband and her two parents. Parental exome data was used to filter potential de novo genomic events in the proband and suspected variants were confirmed using di‐deoxy sequencing. WES revealed a de novo non‐synonymous mutation in exon 21 of the calcium channel gene CACNA1S that has been previously reported in a single patient as a rare cause of atypical hypokalemic periodic paralysis. This was unexpected, as the proband's original differential diagnosis had included hypokalemic periodic paralysis, but clinical and laboratory features were equivocal, and standard clinical molecular testing for hypokalemic periodic paralysis and related disorders was negative. This report highlights the potential diagnostic utility of WES in clinical practice, with implications for the approach to similar diagnostic dilemmas in the future. 相似文献
98.
A. A. Belogurov JR. T. A. Zargarova V. I. Turobov N. I. Novikova O. O. Favorova N. A. Ponomarenko 《Autoimmunity》2013,46(4):362-364
Previously, we demonstrated that autoantibodies (AAb) in multiple sclerosis (MS) reveal site-specific binding and cleavage toward myelin basic protein (MBP) epitope library. We have found several fragments of MBP immunodominant in terms of AAb binding. Here, we applied these peptides to DA rats with induced protracted relapsing experimental allergic encephalomyelitis (EAE) most closely related to MS. DA rats with EAE induced by syngenic spinal cord homogenate in complete Freund's adjuvant were treated by nasal route with human MBP 46–62, 81–102, 124–139, 147–170, and Copaxone®. MBP 124–139 and 147–170 displayed only mild therapeutic effects but MBP 46–62 significantly reduced EAE, reflected by lower clinical scores and shorter EAE duration compared to controls. 相似文献
99.
Expression of hypoxia‐inducible factor‐1α and hepatocyte growth factor in development of fibrosis in the transplanted kidney 下载免费PDF全文
Terese Kellenberger Niels Marcussen Jens R. Nyengaard Lise Wogensen Bente Jespersen 《Transplant international》2015,28(2):180-190
Late renal graft loss is associated with interstitial fibrosis. Hypoxia‐inducible factor‐1α (HIF‐1α) is thought to facilitate fibrosis through interaction with TGF‐β1, while hepatocyte growth factor (HGF) may act antifibrotic in the kidney allograft. The aim of this study was to investigate the expression of HIF‐1α and HGF in protocol biopsies as possible prognostic biomarkers for renal fibrosis. Thirty‐nine renal transplant recipients were included in the study. Protocol biopsies performed 1 and 2 years after transplantation were used for immunohistochemistry analysis. The correlation between HIF‐1α/HGF and the Banff score was analysed. In addition, progression in renal fibrosis and graft survival among recipients with high or low expression of HIF‐1α/HGF after transplantation was compared. There was no significant correlation between fibrosis and the HIF‐1α expression 1 and 2 years after transplantation, but an inverse significant correlation between the HGF expression and the fibrosis score 1 year after transplantation was shown. Even when adjusting for human leucocyte antigen mismatches, there was a significant relationship between fibrosis and HGF expression. Graft survival was not significantly correlated to HIF‐1α or HGF at 1 year, although the trend was towards better graft survival with high HGF. HGF may have antifibrotic effects in human renal transplants. (Central.Denmark.Region.Committee number: 1‐10‐72‐318‐13) 相似文献
100.
Long‐term effectiveness of recommended boosted protease inhibitor‐based antiretroviral therapy in Europe 下载免费PDF全文
JR Santos A Cozzi‐Lepri A Phillips S De Wit C Pedersen P Reiss A Blaxhult A Lazzarin M Sluzhynska C Orkin C Duvivier J Bogner P Gargalianos‐Kakolyris P Schmid G Hassoun I Khromova M Beniowski V Hadziosmanovic D Sedlacek R Paredes JD Lundgren 《HIV medicine》2018,19(5):324-338