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21.
Juul AB Wetterslev J Kofoed-Enevoldsen A Callesen T Jensen G Gluud C;Diabetic Postoperative Mortality Morbidity group 《American heart journal》2004,147(4):677-683
Background
Recent trials suggest that perioperative β-blockade reduces the risk of cardiac events in patients with a risk of myocardial ischemia who are undergoing noncardiac surgery. Patients with diabetes mellitus are at a high-risk for postoperative cardiac morbidity and mortality. They may, therefore, benefit from perioperative β-blockade.Methods
The Diabetic Postoperative Mortality and Morbidity (DIPOM) trial is an investigator-initiated and -controlled, centrally randomized, double-blind, placebo-controlled, multicenter trial. We compared the effect of metoprolol with placebo on mortality and cardiovascular morbidity rates in patients with diabetes mellitus who were β-blocker naive, ≥40 years old, and undergoing noncardiac surgery. The study drug was given during hospitalization for a maximum of 7 days beginning the evening before surgery. The primary outcome measure is the composite of all-cause mortality, acute myocardial infarction, unstable angina, or congestive heart failure leading to hospitalization or discovered or aggravated during hospitalization. Follow-up involves re-examination of patients at 6 months and collection of mortality and morbidity data via linkage to public databases. The study was powered on the basis of an estimated 30% 1-year event rate in the placebo arm and a 33% relative risk reduction in the metoprolol arm. The median follow-up period was 18 months.Results
Enrollment started in July 2000 and ended in June 2002. A total of 921 patients were randomized, and 54% of these patients had known cardiac disease, hypertension, or both.Conclusion
The results of this study may have implications for reduction of perioperative and postoperative risk in patients with diabetes mellitus who are undergoing major noncardiac surgery. 相似文献22.
Acute effects of ghrelin administration on glucose and lipid metabolism 总被引:11,自引:0,他引:11
Vestergaard ET Djurhuus CB Gjedsted J Nielsen S Møller N Holst JJ Jørgensen JO Schmitz O 《The Journal of clinical endocrinology and metabolism》2008,93(2):438-444
CONTEXT: Ghrelin infusion increases plasma glucose and nonesterified fatty acids, but it is uncertain whether this is secondary to the concomitant release of GH. OBJECTIVE: Our objective was to study direct effects of ghrelin on substrate metabolism. DESIGN: This was a randomized, single-blind, placebo-controlled two-period crossover study. SETTING: The study was performed in a university clinical research laboratory. PARTICIPANTS: Eight healthy men aged 27.2 +/- 0.9 yr with a body mass index of 23.4 +/- 0.5 kg/m(2) were included in the study. INTERVENTION: Subjects received infusion of ghrelin (5 pmol x kg(-1) x min(-1)) or placebo for 5 h together with a pancreatic clamp (somatostatin 330 microg x h(-1), insulin 0.1 mU x kg(-1) x min(-1), GH 2 ng x kg(-1) x min(-1), and glucagon 0.5 ng.kg(-1) x min(-1)). A hyperinsulinemic (0.6 mU x kg(-1) x min(-1)) euglycemic clamp was performed during the final 2 h of each infusion. RESULTS: Basal and insulin-stimulated glucose disposal decreased with ghrelin [basal: 1.9 +/- 0.1 (ghrelin) vs. 2.3 +/- 0.1 mg x kg(-1) x min(-1), P = 0.03; clamp: 3.9 +/- 0.6 (ghrelin) vs. 6.1 +/- 0.5 mg x kg(-1) x min(-1), P = 0.02], whereas endogenous glucose production was similar. Glucose infusion rate during the clamp was reduced by ghrelin [4.0 +/- 0.7 (ghrelin) vs. 6.9 +/- 0.9 mg.kg(-1) x min(-1); P = 0.007], whereas nonesterified fatty acid flux increased [131 +/- 26 (ghrelin) vs. 69 +/- 5 micromol/min; P = 0.048] in the basal period. Regional lipolysis (skeletal muscle, sc fat) increased insignificantly with ghrelin infusion. Energy expenditure during the clamp decreased after ghrelin infusion [1539 +/- 28 (ghrelin) vs. 1608 +/- 32 kcal/24 h; P = 0.048], but the respiratory quotient did not differ. Minor but significant elevations in serum levels of GH and cortisol were observed after ghrelin infusion. CONCLUSIONS: Administration of exogenous ghrelin causes insulin resistance in muscle and stimulates lipolysis; these effects are likely to be direct, although a small contribution of GH and cortisol cannot be excluded. 相似文献
23.
Grant S. Lipman David Pomeranz Patrick Burns Caleb Phillips Mary Cheffers Kristina Evans Carrie Jurkiewicz Nick Juul Peter Hackett 《The American journal of medicine》2018,131(2):200.e9-200.e16
Background
Inhaled budesonide has been suggested as a novel prevention for acute mountain sickness. However, efficacy has not been compared with the standard acute mountain sickness prevention medication acetazolamide.Methods
This double-blind, randomized, placebo-controlled trial compared inhaled budesonide versus oral acetazolamide versus placebo, starting the morning of ascent from 1240 m (4100 ft) to 3810 m (12,570 ft) over 4 hours. The primary outcome was acute mountain sickness incidence (headache and Lake Louise Questionnaire ≥3 and another symptom).Results
A total of 103 participants were enrolled and completed the study; 33 (32%) received budesonide, 35 (34%) acetazolamide, and 35 (34%) placebo. Demographics were not different between the groups (P > .09). Acute mountain sickness prevalence was 73%, with severe acute mountain sickness of 47%. Fewer participants in the acetazolamide group (n = 15, 43%) developed acute mountain sickness compared with both budesonide (n = 24, 73%) (odds ratio [OR] 3.5, 95% confidence interval [CI] 1.3-10.1) and placebo (n = 22, 63%) (OR 0.5, 95% CI 0.2-1.2). Severe acute mountain sickness was reduced with acetazolamide (n = 11, 31%) compared with both budesonide (n = 18, 55%) (OR 2.6, 95% CI 1-7.2) and placebo (n = 19, 54%) (OR 0.4, 95% CI 0.1-1), with a number needed to treat of 4.Conclusion
Budesonide was ineffective for the prevention of acute mountain sickness, and acetazolamide was preventive of severe acute mountain sickness taken just before rapid ascent. 相似文献24.
Marthe M. de Jonge Dina Ruano Ronald van Eijk Nienke van der Stoep Maartje Nielsen Juul T. Wijnen Natalja T. ter Haar Astrid Baalbergen Monique E.M.M. Bos Marjolein J. Kagie Maaike P.G. Vreeswijk Katja N. Gaarenstroom Judith R. Kroep Vincent T.H.B.M. Smit Tjalling Bosse Tom van Wezel Christi J. van Asperen 《The Journal of molecular diagnostics : JMD》2018,20(5):600-611
25.
Klomp LW Bull LN Knisely AS van Der Doelen MA Juijn JA Berger R Forget S Nielsen IM Eiberg H Houwen RH 《Hepatology (Baltimore, Md.)》2000,32(6):1337-1341
Greenland familial cholestasis is a severe form of intrahepatic cholestasis described among indigenous Inuit families in Greenland. Patients present with jaundice, pruritus, bleeding episodes, and steatorrhea, and die in childhood due to end-stage liver disease. We investigated the possibility that Greenland familial cholestasis is caused by a mutation in FIC1, the gene defective in patients with progressive familial intrahepatic cholestasis type 1 and many cases of benign recurrent intrahepatic cholestasis. Using single-strand conformation polymorphism analysis and sequencing of the FIC1 exons, a missense mutation, 1660 G-->A (D554N), was detected and was shown to segregate with the disease in Inuit patients from Greenland and Canada. Examination of liver specimens from 3 Inuit patients homozygous for this mutation revealed bland canalicular cholestasis and, on transmission electron microscopy, coarsely granular Byler bile, as previously described in patients with progressive familial intrahepatic cholestasis type 1. These data establish Greenland familial cholestasis as a form of progressive familial intrahepatic cholestasis type 1 and further underscore the importance of unimpeded FIC1 activity for normal bile formation. 相似文献
26.
S. B. Sneppen M. Lange L. M. Pedersen L.
Kristensen K. M. Main A. Juul N. E. Skakkebk U. Feldt-Rasmussen 《Growth hormone & IGF research》2001,11(6):384-391
The aim was to evaluate, markers of disease activity in acromegaly in relation to perceived disease activity. Thirty-seven consecutively treated, acromegalic patients, classified by clinical symptoms as inactive (n=16), slightly active (n=10) and active (n=11), entered the study. When evaluating the inactive and the active groups, we found that positive and negative predictive values (PV(pos), PV(neg)) for clinical disease activity of total and free insulin-like growth factor-I (IGF-I) were 0.59, 0.90 and 1.00, 0.82 respectively. Acid-labile subunit (ALS) showed diagnostic merit similar to insulin-like growth factor binding protein-3 (IGFBP-3) with PV(pos) of 0.69 and 0.71 and PV(neg) of 0.91 and 0.92 respectively. We conclude that free IGF-I is more closely related than total IGF-I to perceived disease activity and is as such useful when evaluating previously treated acromegaly for disease activity. Total IGF-I, IGFBP-3 and ALS possess a higher PV(neg) for the clinical disease activity. None of the parameters can at present be claimed to be superior to the others and thus all the measured parameters are recommended to be part of the evaluation of acromegalic patients. 相似文献
27.
P T Wilmshurst D S Thompson S M Juul B S Jenkins M M Webb-Peploe 《British heart journal》1986,56(6):544-553
The effect of 20 mg dose of intravenous verapamil was studied over a range of heart rates in 12 patients with hypertrophic cardiomyopathy. Six patients had an appreciable left ventricular outflow tract gradient and six did not. The drug reduced myocardial oxygen consumption in proportion to a reduction in the development of left ventricular pressure. The negative inotropic effect of verapamil was counteracted by the drug's non-specific vasodilator activity, so that cardiac index was unaltered at any heart rate and as a result myocardial efficiency was unaffected by the drug. Verapamil did not consistently alter myocardial metabolism. Some patients showed improvement in anaerobic myocardial metabolism after verapamil but an equal number showed impairment of lactate metabolism. It was not possible to predict from clinical features, echocardiographic findings, or haemodynamic variables measured before administration of verapamil which patients would demonstrate haemodynamic or metabolic improvement after the drug. In this short term study no mechanism was demonstrated by which patients with hypertrophic cardiomyopathy might obtain a consistent improvement from treatment with verapamil. 相似文献
28.
Anders Juul Katharina Main Werner F. Blum Jorgen Lindholm Michael B. Ranke Niels E. Skakkebaek 《Clinical endocrinology》1994,41(1):85-93
OBJECTIVE Several in-vitro studies have suggested that the biological actions of IGF-I can be modified by the presence of specific IGF binding proteins. In man, the 24-hour serum levels of IGF-I and IGFBP-3 remain constant, but short-term changes in the IGF-l/IGFBP-3 ratio have been described following GH administration. Serum levels of IGF-I and IGFBP-3 decrease with age in normal adults and are elevated In active acromegaly due to excessive GH secretion. However, the Individual ratios between serum levels of IGF-I and IGFBP-3 in acromegalic and healthy adults have not been described previously. METHODS AND MATERIALS We studied this ratio In 198 healthy adults and In 56 acromegalic patients, grouped according to their serum GH levels (group I GH < 2mLU/l II GH 2–10mLU/l; III GH > 10mLU/l). In all subjects a single blood sample was drawn for IGF-I, IGF-II, IGFBP-1, IGFBP-2, IGFBP-3 and GH measurements by specific RIAs. In 38 of the patients a 24-hour urinary collection was performed for GH determination. RESULTS In healthy adults serum levels of IGF-I and IGFBP-3 decreased with Increasing age (r =?0.52 and r=?0.34, respectively, P< 0.0001). In addition, the molar IGF-l/IGFBP-3 ratio declined with increasing age (r =?0.44, P – 0.0001). In patients with acromegaly and high serum GH levels (group III), circulating IGF-I was increased 7–97 standard deviations (SDS) and IGFBP-3 was increased 4.20 SOS (P < 0.0001). Serum levels of IGF-II were normal in all three groups (588 ± 240μ/l) whereas IGFBP-1 and IGFBP-2 levels were low and IGFBP-2 levels decreased significantly with increasing serum GH levels (P < 0.0001). The molar IGF-l/IGFBP-3 ratio in the acromegalic patients was significantly higher than in the controls (P < 0.0001) and correlated significantly with urinary GH excretion (r = 0.67, P < 0.0001) as well as with serum GH levels (r = 0.73, P < 0.0001). CONCLUSION We demonstrated a decreasing molar IGF-l/IGFBP-3 ratio with increasing age in healthy adults and an increased ratio between serum IGF-I and IGFBP-3 levels in acromegalic patients. As IGF-II is normal and IGFBP-1 and IGFBP-2 are inversely correlated to the serum GH levels In the acromegalic patients, we speculate that the molar ratio between IGF-I and IGFBP-3 reflects free (biologically active) IGF-I and Is dependent on GH levels. 相似文献
29.
Resveratrol reduces the levels of circulating androgen precursors but has no effect on,testosterone, dihydrotestosterone,PSA levels or prostate volume. A 4‐month randomised trial in middle‐aged men 下载免费PDF全文
30.
Acute haemodynamic and metabolic effects of dopexamine, a new dopaminergic receptor agonist, in patients with chronic heart failure. 下载免费PDF全文
J R Dawson D S Thompson M Signy S M Juul P Turnbull B S Jenkins M M Webb-Peploe 《Heart (British Cardiac Society)》1985,54(3):313-320
Dopexamine, a new compound with postjunctional dopamine receptor activating and beta adrenoceptor agonist properties, was given to 10 patients with chronic heart failure at diagnostic cardiac catheterisation to investigate its acute haemodynamic and metabolic effects. The drug was administered by intravenous infusion in three incremental doses and produced significant dose related increases in cardiac index, stroke volume index, and heart rate and falls in systemic vascular resistance and left ventricular end diastolic pressure; aortic and pulmonary artery pressures were unchanged. Isovolumic phase (max dP/dt and KVmax) and ejection phase (peak aortic blood velocity, maximum acceleration of blood, and maximum rate of change of power with time during ejection) indices of myocardial contractility were all increased by dopexamine but these changes were hard to interpret in the presence of an increase in heart rate. Myocardial efficiency and ejection fraction were both increased and left ventricular end diastolic and end systolic volumes fell. These largely beneficial changes were achieved without a statistically significant increase in myocardial oxygen consumption or disturbance of myocardial metabolic function. Dopexamine was well tolerated but tremor was reported by two patients at the intermediate dose and mild chest pain by two patients at the high dose. 相似文献