全文获取类型
收费全文 | 94篇 |
免费 | 9篇 |
国内免费 | 3篇 |
专业分类
耳鼻咽喉 | 1篇 |
儿科学 | 3篇 |
基础医学 | 19篇 |
口腔科学 | 3篇 |
临床医学 | 8篇 |
内科学 | 31篇 |
特种医学 | 13篇 |
外科学 | 9篇 |
综合类 | 4篇 |
预防医学 | 2篇 |
眼科学 | 2篇 |
药学 | 5篇 |
肿瘤学 | 6篇 |
出版年
2022年 | 2篇 |
2020年 | 2篇 |
2018年 | 2篇 |
2017年 | 1篇 |
2016年 | 2篇 |
2015年 | 2篇 |
2014年 | 5篇 |
2013年 | 4篇 |
2012年 | 4篇 |
2011年 | 5篇 |
2010年 | 5篇 |
2009年 | 6篇 |
2008年 | 5篇 |
2007年 | 4篇 |
2006年 | 3篇 |
2005年 | 3篇 |
2004年 | 6篇 |
2003年 | 4篇 |
2002年 | 7篇 |
2001年 | 1篇 |
2000年 | 2篇 |
1999年 | 1篇 |
1998年 | 4篇 |
1997年 | 8篇 |
1996年 | 3篇 |
1995年 | 3篇 |
1994年 | 1篇 |
1990年 | 1篇 |
1988年 | 2篇 |
1986年 | 1篇 |
1985年 | 1篇 |
1984年 | 1篇 |
1981年 | 2篇 |
1978年 | 1篇 |
1977年 | 2篇 |
排序方式: 共有106条查询结果,搜索用时 15 毫秒
41.
Cholangiocytes, the epithelial cells lining intrahepatic bile ducts, are ciliated cells. Each cholangiocyte has a primary cilium consisting of (i) a microtubule-based axoneme and (ii) the basal body, centriole-derived, microtubule-organizing center from which the axoneme emerges. Primary cilia in cholangiocytes were described decades ago, but their physiological and pathophysiological significance remained unclear until recently. We now recognize that cholangiocyte cilia extend from the apical plasma membrane into the bile duct lumen and, as such, are ideally positioned to detect changes in bile flow, bile composition and bile osmolality. These sensory organelles act as cellular antennae that can detect and transmit signals that influence cholangiocyte function. Indeed, recent data show that cholangiocyte primary cilia can activate intracellular signaling pathways when they sense modifications in the flow, molecular constituents and osmolarity of bile. Their ability to sense and transmit signals depends on the participation of a growing number of specific ciliary-associated proteins that act as receptors, channels and transporters. Cholangiocyte cilia, in addition to being important in normal biliary physiology, likely contribute to the cholangiopathies when their normal structure or function is disturbed. Indeed, the polycystic liver diseases that occur in combination with autosomal dominant and recessive polycystic kidney disease (i.e. ADPKD and ARPKD) are two important examples of such conditions. Recent insights into the role of cholangiocyte cilia in cystic liver disease using in vitro and animal models have already resulted in clinical trials that have influenced the management of cystic liver disease. 相似文献
42.
43.
Gradilone SA Masyuk AI Splinter PL Banales JM Huang BQ Tietz PS Masyuk TV Larusso NF 《Proceedings of the National Academy of Sciences of the United States of America》2007,104(48):19138-19143
Cholangiocytes, epithelial cells lining the biliary tree, have primary cilia extending from their apical membrane into the ductal lumen. Although important in disease, cilia also play a vital role in normal cellular functions. We reported that cholangiocyte cilia are sensory organelles responding to mechanical stimuli (i.e., luminal fluid flow) by alterations in intracellular Ca(2+) and cAMP. Because cholangiocyte cilia are also ideally positioned to detect changes in composition and tonicity of bile, we hypothesized that cilia also function as osmosensors. TRPV4, a Ca(2+)-permeable ion channel, has been implicated in signal transduction of osmotic stimuli. Using purified rat cholangiocytes and perfused intrahepatic bile duct units (IBDUs), we found that TRPV4 is expressed on cholangiocyte cilia, and that hypotonicity induces an increase in intracellular Ca(2+) in a TRPV4-, ciliary-, and extracellular calcium-dependent manner. The osmosensation of luminal tonicity by ciliary TRPV4 induces bicarbonate secretion, the main determinant of ductal bile formation, by a mechanism involving apical ATP release. Furthermore, the activation of TRPV4 in vivo, by its specific agonist, 4alphaPDD, induces an increase in bile flow as well as ATP release and bicarbonate secretion. Our results suggest that cholangiocyte primary cilia play an important role in ductal bile formation by acting as osmosensors. 相似文献
44.
Marie C. Hogan Tetyana V. Masyuk Linda J. Page Vickie J. Kubly Eric J. Bergstralh Xujian Li Bohyun Kim Bernard F. King James Glockner David R. Holmes III Sandro Rossetti Peter C. Harris Nicholas F. LaRusso Vicente E. Torres 《Journal of the American Society of Nephrology : JASN》2010,21(6):1052-1061
There are no proven, effective therapies for polycystic kidney disease (PKD) or polycystic liver disease (PLD). We enrolled 42 patients with severe PLD resulting from autosomal dominant PKD (ADPKD) or autosomal dominant PLD (ADPLD) in a randomized, double-blind, placebo-controlled trial of octreotide, a long-acting somatostatin analogue. We randomly assigned 42 patients in a 2:1 ratio to octreotide LAR depot (up to 40 mg every 28 ± 5 days) or placebo for 1 year. The primary end point was percent change in liver volume from baseline to 1 year, measured by MRI. Secondary end points were changes in total kidney volume, GFR, quality of life, safety, vital signs, and clinical laboratory tests. Thirty-four patients had ADPKD, and eight had ADPLD. Liver volume decreased by 4.95% ± 6.77% in the octreotide group but remained practically unchanged (+0.92% ± 8.33%) in the placebo group (P = 0.048). Among patients with ADPKD, total kidney volume remained practically unchanged (+0.25% ± 7.53%) in the octreotide group but increased by 8.61% ± 10.07% in the placebo group (P = 0.045). Changes in GFR were similar in both groups. Octreotide was well tolerated; treated individuals reported an improved perception of bodily pain and physical activity. In summary, octreotide slowed the progressive increase in liver volume and total kidney volume, improved health perception among patients with PLD, and had an acceptable side effect profile.Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the development of renal cysts and a variety of extrarenal manifestations of which polycystic liver disease (PLD) is the most common.1 It is caused by mutations in one of two genes: PKD1 or PKD2. PKD1 mutations are responsible for approximately 85% of clinically detected cases. Autosomal dominant PLD (ADPLD) also exists as a genetically distinct disease with few or absent renal cysts. Like ADPKD, ADPLD is genetically heterogeneous, with the first two genes identified (PRKCSH and SEC63) accounting for approximately one-third to one-half of isolated ADPLD cases.2–5Chronic symptoms are frequently associated with massively enlarged PLD, including abdominal distension and pain, dyspnea, gastroesophageal reflux, and early satiety, which may lead to malnutrition, mechanical lower back pain, inferior vena cava, hepatic and portal vein compression (leading to hypotension and inferior vena cava thrombosis, hepatic venous outflow obstruction, and portal hypertension), and biliary obstruction. Surgical approaches may be associated with definitive palliation but are also associated with a risk of morbidity and mortality.6Liver cysts arise by excessive proliferation of cholangiocytes and dilation of biliary ductules and peribiliary glands. Alterations in intracellular calcium homeostasis and 3′-5′-cAMP stimulate mitogen-activated protein kinase-mediated cell proliferation and cystic fibrosis transmembrane conductance regulator-driven chloride and fluid secretion.7 Cyst growth is enhanced by growth factors and cytokines secreted into the cyst fluid.8 Downstream activation of mTOR likely contributes to cystogenesis.9 Somatostatin may blunt cyst development by acting at multiple levels: inhibition of secretin release by the pancreas10; inhibition of secretin-induced cAMP generation and fluid secretion in cholangiocytes11–13; vasopressin-induced cAMP generation and water permeability in collecting ducts14–17 by its effects on Gi protein-coupled receptors; and suppression of the expression of IGF-1, vascular endothelial growth factor, and other cystogenic growth factors and of downstream signaling from their receptors.14–18To determine whether octreotide could be effective in the treatment of PLD, we examined the effects of octreotide in the PCK rat, a recessive model of polycystic liver and kidney disease. We found that octreotide significantly reduced cAMP levels and hepatic cystogenesis in vitro and in vivo.19 In patients who underwent liver resections for massive PLD, we had observed that administration of octreotide reduced the rate of fluid secretion from unroofed cysts. In one patient with persistent ascites, intramuscular administration of octreotide LAR 40 mg monthly for 8 months was accompanied by a 17.8% reduction in liver volume from 2833 ml to 2330 ml (Figure 1). Two similar instances have been recently reported by van Keimpema et al.20 Finally, a pilot study showed that administration of octreotide LAR significantly inhibited kidney and cyst enlargement in patients with ADPKD.21 Encouraged by the results of the preclinical studies, anecdotal clinical experiences, and the pilot study in ADPKD, we initiated a pilot randomized, placebo-controlled, double-blind clinical trial of octreotide LAR in severe PLD.Open in a separate windowFigure 1.Administration of octreotide LAR to a patient with severe PLD resulted in decreased liver and kidney volumes. CT axial sections immediately before (A) and after 8 months of treatment with octreotide (B) are shown. Total liver volume decreased by 18% from baseline, and total kidney volume decreased by 12%. 相似文献
45.
46.
本研究旨在确定服用口服避孕药的女.胜其死亡风险是否高于未服用者。本次前瞻性试验研究,由英国全科医生资料库和(或)国家健康服务中心登记处提供始于1968年的死亡资料,对46112位女性持续观察了39年,其中未使用口服避孕药的女性为378006人年,曾服用者为819175人年,主要观察终点未口服和口服避孕药者之间全因和特异性死亡的相对风险。 相似文献
47.
OBJECTIVE: To describe the epidemiology of air gun injuries to children that required hospitalization. DESIGN: A consecutive series of children with air gun injuries. SETTING: Urban pediatric teaching hospitals in Cincinnati, OH; Kansas City, MO; and Seattle, WA. METHODS: A retrospective chart review. RESULTS: A total of 101 children were studied: 81% were male; 80% were white, 18% were black, and 2% were other races. The median age was 10.9 years (range, 0.5 to 18.8). Victims were most commonly shot by a friend (30%) or sibling (21%). A total of 34% occurred at the victim's home, and 36% occurred at the home of a friend or relative. Although 71% of shootings were unintentional, 5% were assaults, and 1% were suicides. The median hospital stay was 3 days (range, 1 to 17 days). Fifteen children (15%) required treatment in intensive care. A total of 56% required at least one surgical procedure. Forty-nine had injuries to the head, including 38 with injuries to the eye, 10 with intracranial injuries, and 1 with a skull injury. Fourteen children were shot in the neck; 15 were shot in the chest, with 2 patients sustaining lacerations of the pericardium and 1 having a right ventricular foreign body. Another child had a laceration of the innominate artery. Nineteen had abdominal injuries, including laceration of the stomach (N = 3), small bowel (N = 4), colon (N = 2), and liver (N = 3). Three of 10 children with intracranial injuries died. Two had long-term neurologic deficits. Of children with eye injuries, 25 (66%) had permanent visual loss and 15 (39%) of these were blind. CONCLUSION: Air guns are associated with serious and fatal injuries. Families should be counseled that air guns may cause serious injuries and even death. Furthermore, pediatric care givers should advocate for increased regulation of air guns and expansion of safety standards. 相似文献
48.
Proliferation, differentiation, and cytogenetics of chronic leukemic B lymphocytes cultured with mitomycin-treated normal cells 总被引:10,自引:0,他引:10
Lymphocytes from 6 patients with chronic lymphocytic leukemia of the B- cell variety (B-CLL) were cultured with equal numbers of mitomycin- treated mononuclear cells from normal blood. When stimulated with pokeweed mitogen (PWM), phytohemagglutinin (PHA), or the tumor- promoting agent, phorbol tetradecanoyl-acetate (TPA), the CLL cells proliferated actively by day 3 or 4 of culture, and in four cases, differentiated to significant numbers of immunoglobulin-containing cells. Chromosome studies on the proliferating lymphocytes demonstrated a cytogenetically abnormal clone in three patients, including two with a 14q+ marker chromosome and two with a translocation involving the short arm of chromosome 9. One patient had a translocation from 22q to 14q, producing a Philadelphia chromosome as well as the 14q+ marker. The results indicate that the neoplastic lymphocytes of B-CLL may proliferate and differentiate when appropriately stimulated in vitro, and that chromosomally abnormal clones are not uncommon. With several techniques now available for successful short-term culture of B-CLL lymphocytes, there is opportunity for better understanding of the cellular alterations in this disease. 相似文献
49.
Inhibition of Cdc25A suppresses hepato-renal cystogenesis in rodent models of polycystic kidney and liver disease 总被引:1,自引:0,他引:1
50.