全文获取类型
收费全文 | 455篇 |
免费 | 45篇 |
国内免费 | 1篇 |
专业分类
耳鼻咽喉 | 1篇 |
儿科学 | 15篇 |
妇产科学 | 8篇 |
基础医学 | 40篇 |
口腔科学 | 9篇 |
临床医学 | 30篇 |
内科学 | 115篇 |
皮肤病学 | 9篇 |
神经病学 | 19篇 |
特种医学 | 2篇 |
外科学 | 48篇 |
综合类 | 7篇 |
一般理论 | 2篇 |
预防医学 | 30篇 |
眼科学 | 17篇 |
药学 | 43篇 |
中国医学 | 3篇 |
肿瘤学 | 103篇 |
出版年
2024年 | 1篇 |
2023年 | 9篇 |
2022年 | 16篇 |
2021年 | 23篇 |
2020年 | 17篇 |
2019年 | 22篇 |
2018年 | 24篇 |
2017年 | 24篇 |
2016年 | 15篇 |
2015年 | 17篇 |
2014年 | 33篇 |
2013年 | 27篇 |
2012年 | 36篇 |
2011年 | 37篇 |
2010年 | 22篇 |
2009年 | 18篇 |
2008年 | 26篇 |
2007年 | 28篇 |
2006年 | 25篇 |
2005年 | 27篇 |
2004年 | 29篇 |
2003年 | 11篇 |
2002年 | 11篇 |
1999年 | 1篇 |
1998年 | 1篇 |
1997年 | 1篇 |
排序方式: 共有501条查询结果,搜索用时 19 毫秒
91.
Reshma Amin Andrea Riekstins Suhail Al-Saleh Colin Massicotte Allan L Coates Ian MacLusky 《Canadian respiratory journal》2011,18(2):87-89
Congenital central hypoventilation syndrome is a rare genetic disorder characterized by hypoventilation during sleep secondary to a blunted response to hypercapnia and hypoxia. The current case report describes developmentally normal four-year-old monozygotic twin boys who presented in infancy with variable presentations and clinical severity of congenital central hypoventilation syndrome. Both were managed with noninvasive positive pressure ventilation. 相似文献
92.
Reshma Ramracheya Caroline Ward Makoto Shigeto Jonathan N. Walker Stefan Amisten Quan Zhang Paul R. Johnson Patrik Rorsman Matthias Braun 《Diabetes》2010,59(9):2198-2208
OBJECTIVE
To document the properties of the voltage-gated ion channels in human pancreatic α-cells and their role in glucagon release.RESEARCH DESIGN AND METHODS
Glucagon release was measured from intact islets. [Ca2+]i was recorded in cells showing spontaneous activity at 1 mmol/l glucose. Membrane currents and potential were measured by whole-cell patch-clamping in isolated α-cells identified by immunocytochemistry.RESULTS
Glucose inhibited glucagon secretion from human islets; maximal inhibition was observed at 6 mmol/l glucose. Glucagon secretion at 1 mmol/l glucose was inhibited by insulin but not by ZnCl2. Glucose remained inhibitory in the presence of ZnCl2 and after blockade of type-2 somatostatin receptors. Human α-cells are electrically active at 1 mmol/l glucose. Inhibition of KATP-channels with tolbutamide depolarized α-cells by 10 mV and reduced the action potential amplitude. Human α-cells contain heteropodatoxin-sensitive A-type K+-channels, stromatoxin-sensitive delayed rectifying K+-channels, tetrodotoxin-sensitive Na+-currents, and low-threshold T-type, isradipine-sensitive L-type, and ω-agatoxin-sensitive P/Q-type Ca2+-channels. Glucagon secretion at 1 mmol/l glucose was inhibited by 40–70% by tetrodotoxin, heteropodatoxin-2, stromatoxin, ω-agatoxin, and isradipine. The [Ca2+]i oscillations depend principally on Ca2+-influx via L-type Ca2+-channels. Capacitance measurements revealed a rapid (<50 ms) component of exocytosis. Exocytosis was negligible at voltages below −20 mV and peaked at 0 mV. Blocking P/Q-type Ca2+-currents abolished depolarization-evoked exocytosis.CONCLUSIONS
Human α-cells are electrically excitable, and blockade of any ion channel involved in action potential depolarization or repolarization results in inhibition of glucagon secretion. We propose that voltage-dependent inactivation of these channels underlies the inhibition of glucagon secretion by tolbutamide and glucose.Glucagon is the principal hyperglycemic hormone (1,2). It is secreted from the pancreatic α-cells in response to a fall in plasma glucose levels, β-adrenergic stimulation, lipids, and amino acids (3–5). Glucagon secretion from α-cells is regulated by paracrine (3), neuronal (6), and intrinsic mechanisms (7). Diabetes involves both impaired insulin and glucagon secretion (8). Thus, hyperglucagonemia is thought to contribute to elevated blood glucose levels, and the impaired glucagon response to hypoglycemia represents a limiting factor for insulin treatment in both type 1 and type 2 diabetes (9,10).Ion channels and electrical activity play a key role in the regulation of glucagon secretion. The properties of rodent α-cells have been characterized in some detail (5,11–13). Rodent α-cells are electrically excitable and electrically active in the absence of glucose. Action potential firing depends on the opening of voltage-activated L- and N-type Ca2+-channels, tetrodotoxin (TTX)-sensitive Na+-channels, and A-type K+-channels (14).The α-cells make up ∼35% of the cell population in human islets (15,16). Here, we have characterized the electrophysiological properties of isolated human α-cells and correlated our findings to changes in glucagon secretion from intact human islets. Our data indicate that glucagon secretion depends on a complex interplay among a number of depolarizing and repolarizing membrane currents. 相似文献93.
94.
Amin R Ford-Jones E Richardson SE MacGregor D Tellier R Heurter H Fearon M Bitnun A 《The Pediatric infectious disease journal》2008,27(5):390-395
BACKGROUND: Influenza virus infection has been associated with a variety of neurologic complications. The objective of this study was to evaluate prospectively the role of influenza viruses in acute childhood encephalitis/encephalopathy (ACE). METHODS: All children admitted to the Hospital for Sick Children, Toronto, during an 11-year period with ACE and evidence of acute influenza virus infection were included. Acute influenza virus infection was defined by detection of the organism in the nasopharynx by direct immunofluorescence microscopy or viral culture and/or by a 4-fold or greater rise in complement fixation titer. RESULTS: A total of 311 children with ACE were evaluated; evidence of influenza infection was detected in 7% (22 of 311). Eight were excluded from the main analysis because of evidence implicating other potential pathogens. Eleven of the 14 included subjects were <5 years of age. A respiratory prodrome was documented in 93% of subjects. In 64% neurologic manifestations developed within 5 days of onset of respiratory symptoms. Neuroimaging abnormalities were more common in children <2 years of age. Neurologic sequelae occurred in more than one-half of subjects. CONCLUSIONS: In this prospective registry, influenza virus infection was associated with 5% of ACE cases. The majority of children were <5 years of age and the prevalence of neuroimaging abnormalities was higher in children <2 years of age suggesting that younger children are predisposed to the neurologic complications of influenza. An acute rather than a postinfectious process was suggested by the briefness of the respiratory prodrome in most cases. 相似文献
95.
96.
97.
Abdulrahman O. Musaiger Reshma D'Souza Jassim H. Al-Jedah 《Ecology of food and nutrition》2013,52(6):518-530
An evaluation of seven confectionery items commonly consumed in the Arabian Gulf region is presented with regard to their nutritional profiles. The foods contained 1.1–17.3% (N × 6.25) protein, 41.8–81.2% carbohydrate and 6.3–38.8% w/w fat. Some dominant minerals were sodium (685–6152 ppm), potassium (237–9507 ppm) and magnesium (68–1650 ppm). β sitosterol ranged between 4.4–95.9 mg/100g, and cholesterol was high (55.0 mg/100g) in the sesame based sweet. The prominent fatty acids were oleic (31.5–54.8 mg/100g) and linoleic acid (16.5–52.9 mg/100g). Regional dietary guidelines should take into consideration the nutritive value and health aspects of traditional confections which should be consumed in moderation, due to their high content of fat, cholesterol and sugar. 相似文献
98.
Design and Development of Mycobacterium tuberculosis Lysine ɛ‐Aminotransferase Inhibitors for Latent Tuberculosis Infection
下载免费PDF全文
![点击此处可从《Chemical biology & drug design》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Brindha Devi Parthiban Shalini Saxena Manoj Chandran Padma Sridevi Jonnalagadda Renu Yadav Rudraraju Reshma Srilakshmi Yogeeswari Perumal Sriram Dharmarajan 《Chemical biology & drug design》2016,87(2):265-274
Lysine ?‐aminotransferase (LAT) is a protein involved in lysine catabolism, and it plays a significant role during the persistent/latent phase of Mycobacterium tuberculosis (MTB), as observed by its up‐regulation by ~40‐fold during this stage. We have used the crystal structure of MTB LAT in external aldimine form in complex with its substrate lysine as a template to design and identify seven lead compounds with IC50 ranging from 18.06 to > 90 μm . We have synthesized 21 compounds based on the identified lead, and compound 21 [2,2′‐oxybis(N′‐(4‐fluorobenzylidene)acetohydrazide)] was found to be the most active with MTB LAT IC50 of 0.81 ± 0.03 μm . Compound 21 also showed a 2.3 log reduction in the nutrient‐starved MTB model and was more potent than standard isoniazid and rifampicin at the same dose level of 10 μg/mL. 相似文献
99.
100.
Impact of adjuvant chemotherapy on long‐term employment of survivors of early‐stage breast cancer
下载免费PDF全文
![点击此处可从《Cancer》网站下载免费的PDF全文](/ch/ext_images/free.gif)