全文获取类型
收费全文 | 621篇 |
免费 | 54篇 |
国内免费 | 2篇 |
出版年
2023年 | 5篇 |
2022年 | 11篇 |
2021年 | 14篇 |
2020年 | 4篇 |
2019年 | 1篇 |
2018年 | 9篇 |
2017年 | 6篇 |
2016年 | 28篇 |
2015年 | 85篇 |
2014年 | 60篇 |
2013年 | 58篇 |
2012年 | 101篇 |
2011年 | 77篇 |
2010年 | 32篇 |
2009年 | 23篇 |
2008年 | 26篇 |
2007年 | 18篇 |
2006年 | 14篇 |
2005年 | 14篇 |
2004年 | 8篇 |
2003年 | 13篇 |
2002年 | 20篇 |
2001年 | 7篇 |
2000年 | 5篇 |
1999年 | 2篇 |
1998年 | 3篇 |
1997年 | 1篇 |
1991年 | 1篇 |
1988年 | 1篇 |
1987年 | 2篇 |
1986年 | 4篇 |
1984年 | 4篇 |
1983年 | 1篇 |
1981年 | 1篇 |
1979年 | 2篇 |
1978年 | 1篇 |
1977年 | 2篇 |
1974年 | 1篇 |
1973年 | 4篇 |
1970年 | 1篇 |
1968年 | 7篇 |
排序方式: 共有677条查询结果,搜索用时 343 毫秒
1.
2.
Prostaglandins have been hypothesized to have several mechanistic functions in sympathetically mediated release of renin. The rabbit renal cortical slice system was chosen to examine the prostaglandin dependency of renin release directly stimulated by either a direct adenylate cyclase activator, forskolin, or a β-agonist, isoproterenol. In this study, we demonstrate that with forskolin (1 × 10−5M) or isoproterenol (1 × 10−6M), renin release was elevated 2–3 fold above control, and that this increase was shown to accompany a substantial increase in the tissue levels f cAMP (19.5 fold and 3.5 fold respectively). We also demonstrate that the increase in renin release produced by these compounds was not inhibited by cyclooxygenase inhibitors, indomethacin (25 uM) or eicosatetraynoic acid (30 ug/ml), nor was it inhibited by the selective prostacyclin synthesis inhibitor, U-51605 (30 ug/ml). Each of these inhibitors was demonstrated to block the synthesis of prostaglandins in the cortical slices at the concentrations used. Thus we propose that prostaglandins do not play a role in the induction of renin release resulting from elevated cyclic nucleotide levels or β-adrenergic stimulation. 相似文献
3.
L Pilotti P G Data G Di Tano 《Bollettino della Società italiana di biologia sperimentale》1984,60(10):1885-1890
In this study was investigated the diagnostic significance of double stimulation test with (that is of 25 micrograms rapid injection intravenously twice at an interval of 120 minutes and the misure of maximal net increment of serum LH after the first GnRH injection expressed as delta 1 and after the second injection, expressed as delta 2) to discriminate patients with idiopatic hirsutism. This test was effectuated on 8 patients with PCO (presence of polycystic ovaries on Ecografya and/or Laparoscopy) and 8 patients with idiopatic hirsutism (presence of normal morphology ovaries). Basal LH, FSH, E1, E2 and delta 4 levels were also measured. The value of LH delta 2 were more elevated in patients with PCO (p less than 0,0002) than the patients with idiopatic hirsutism. Consequently it as been value of LH delta 2 to discriminate the two different groups of patients. In PCO patients were also found: -a positive linear correlation between LH delta 1 and basal concentration serum of E2 (p less than 0,001); -a significant increase of basal levels serum of delta 4 (p less than 0,02); while the values of basal LH and LH delta 1 were found superior only on 4 of the initial 8 patients, the basal values of E1 and E2 were at the superior found of the norm and basal FSH, FSH delta 1 and FSH delta 2 values were found normals. 相似文献
4.
G.Christian Friesinger Oswald Oelz Brian J. Sweetman Alan S. Nies Joann L. Data 《Prostaglandins & other lipid mediators》1978,15(6):969-981
Prostaglandin (PG) D2 was biosynthesized by rabbit renal papillae incubates in vitro. Quantification of the renal prostaglandins by gas chromatography-mass spectroscopy demonstrated that the concentration of PGD2 generated by renal papillae was
to
the amount of PGE2 or about 1 μg/g tissue/30 min. Infusion of the sodium salt of PGD2 into the renal artery of the dog produced a dose related increase in renal blood flow and urine flow, free water clearance, sodium excretion and potassium excretion without changes in systemic hemodynamics. At low doses PGD2 increased renal blood flow to all cortical zones. Higher concentrations of PGD2 produced a shift in the intrarenal distribution of blood flow toward the juxtamedullary nephrons. 相似文献
5.
6.
7.
Sumit Mohan Edwin Huff Jay Wish Michael Lilly Shu-Cheng Chen William M. McClellan for the Fistula First Breakthrough Initiative Data Committee 《PloS one》2013,8(12)
Background
Patients started on long term hemodialysis have typically had low rates of reported renal recovery with recent estimates ranging from 0.9–2.4% while higher rates of recovery have been reported in cohorts with higher percentages of patients with acute renal failure requiring dialysis.Study Design
Our analysis followed approximately 194,000 patients who were initiated on hemodialysis during a 2-year period (2008 & 2009) with CMS-2728 forms submitted to CMS by dialysis facilities, cross-referenced with patient record updates through the end of 2010, and tracked through December 2010 in the CMS SIMS registry.Results
We report a sustained renal recovery (i.e no return to ESRD during the available follow up period) rate among Medicare ESRD patients of > 5% - much higher than previously reported. Recovery occurred primarily in the first 2 months post incident dialysis, and was more likely in cases with renal failure secondary to etiologies associated with acute kidney injury. Patients experiencing sustained recovery were markedly less likely than true long-term ESRD patients to have permanent vascular accesses in place at incident hemodialysis, while non-White patients, and patients with any prior nephrology care appeared to have significantly lower rates of renal recovery. We also found widespread geographic variation in the rates of renal recovery across the United States.Conclusions
Renal recovery rates in the US Medicare ESRD program are higher than previously reported and appear to have significant geographic variation. Patients with diagnoses associated with acute kidney injury who are initiated on long-term hemodialysis have significantly higher rates of renal recovery than the general ESRD population and lower rates of permanent access placement. 相似文献8.
Irene Pichler Fabiola Del Greco M. Martin G?gele Christina M. Lill Lars Bertram Chuong B. Do Nicholas Eriksson Tatiana Foroud Richard H. Myers PD GWAS Consortium Michael Nalls Margaux F. Keller International Parkinson's Disease Genomics Consortium Wellcome Trust Case Control Consortium Beben Benyamin John B. Whitfield Genetics of Iron Status Consortium Peter P. Pramstaller Andrew A. Hicks John R. Thompson Cosetta Minelli 《PLoS medicine》2013,10(6)
Background
Although levels of iron are known to be increased in the brains of patients with Parkinson disease (PD), epidemiological evidence on a possible effect of iron blood levels on PD risk is inconclusive, with effects reported in opposite directions. Epidemiological studies suffer from problems of confounding and reverse causation, and mendelian randomization (MR) represents an alternative approach to provide unconfounded estimates of the effects of biomarkers on disease. We performed a MR study where genes known to modify iron levels were used as instruments to estimate the effect of iron on PD risk, based on estimates of the genetic effects on both iron and PD obtained from the largest sample meta-analyzed to date.Methods and Findings
We used as instrumental variables three genetic variants influencing iron levels, HFE rs1800562, HFE rs1799945, and TMPRSS6 rs855791. Estimates of their effect on serum iron were based on a recent genome-wide meta-analysis of 21,567 individuals, while estimates of their effect on PD risk were obtained through meta-analysis of genome-wide and candidate gene studies with 20,809 PD cases and 88,892 controls. Separate MR estimates of the effect of iron on PD were obtained for each variant and pooled by meta-analysis. We investigated heterogeneity across the three estimates as an indication of possible pleiotropy and found no evidence of it. The combined MR estimate showed a statistically significant protective effect of iron, with a relative risk reduction for PD of 3% (95% CI 1%–6%; p = 0.001) per 10 µg/dl increase in serum iron.Conclusions
Our study suggests that increased iron levels are causally associated with a decreased risk of developing PD. Further studies are needed to understand the pathophysiological mechanism of action of serum iron on PD risk before recommendations can be made. Please see later in the article for the Editors'' Summary 相似文献9.
Sophie Garnier Vinh Truong Jessy Brocheton Tanja Zeller Maxime Rovital Philipp S. Wild Andreas Ziegler The Cardiogenics Consortium Thomas Munzel Laurence Tiret Stefan Blankenberg Panos Deloukas Jeannette Erdmann Christian Hengstenberg Nilesh J. Samani Heribert Schunkert Willem H. Ouwehand Alison H. Goodall Fran?ois Cambien David-Alexandre Trégou?t 《PLoS genetics》2013,9(1)
10.
Michael?R. Knowles Margaret?W. Leigh Lawrence?E. Ostrowski Lu Huang Johnny?L. Carson Milan?J. Hazucha Weining Yin Jonathan?S. Berg Stephanie?D. Davis Sharon?D. Dell Thomas?W. Ferkol Margaret Rosenfeld Scott?D. Sagel Carlos?E. Milla Kenneth?N. Olivier Emily?H. Turner Alexandra?P. Lewis Michael?J. Bamshad Deborah?A. Nickerson Jay Shendure Maimoona?A. Zariwala the Genetic Disorders of Mucociliary Clearance?Consortium 《American journal of human genetics》2013,92(1):99-106
Primary ciliary dyskinesia (PCD) is a genetically heterogeneous, autosomal-recessive disorder, characterized by oto-sino-pulmonary disease and situs abnormalities. PCD-causing mutations have been identified in 14 genes, but they collectively account for only ∼60% of all PCD. To identify mutations that cause PCD, we performed exome sequencing on six unrelated probands with ciliary outer dynein arm (ODA) defects. Mutations in CCDC114, an ortholog of the Chlamydomonas reinhardtii motility gene DCC2, were identified in a family with two affected siblings. Sanger sequencing of 67 additional individuals with PCD with ODA defects from 58 families revealed CCDC114 mutations in 4 individuals in 3 families. All 6 individuals with CCDC114 mutations had characteristic oto-sino-pulmonary disease, but none had situs abnormalities. In the remaining 5 individuals with PCD who underwent exome sequencing, we identified mutations in two genes (DNAI2, DNAH5) known to cause PCD, including an Ashkenazi Jewish founder mutation in DNAI2. These results revealed that mutations in CCDC114 are a cause of ciliary dysmotility and PCD and further demonstrate the utility of exome sequencing to identify genetic causes in heterogeneous recessive disorders. 相似文献