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71.
E Katriina Tarkiainen Aleksi Tornio Mikko T Holmberg Terhi Launiainen Pertti J Neuvonen Janne T Backman Mikko Niemi 《British journal of clinical pharmacology》2015,80(5):1131-1138
Aim
The aim of the present study was to investigate the effects of the carboxylesterase 1 (CES1) c.428G > A (p.G143E, rs71647871) single nucleotide variation (SNV) on the pharmacokinetics of quinapril and enalapril in a prospective genotype panel study in healthy volunteers.Methods
In a fixed-order crossover study, 10 healthy volunteers with the CES1 c.428G/A genotype and 12 with the c.428G/G genotype ingested a single 10 mg dose of quinapril and enalapril with a washout period of at least 1 week. Plasma concentrations of quinapril and quinaprilat were measured for up to 24 h and those of enalapril and enalaprilat for up to 48 h. Their excretion into the urine was measured from 0 h to 12 h.Results
The area under the plasma concentration–time curve from 0 h to infinity (AUC0–∞) of active enalaprilat was 20% lower in subjects with the CES1 c.428G/A genotype than in those with the c.428G/G genotype (95% confidence interval of geometric mean ratio 0.64, 1.00; P = 0.049). The amount of enalaprilat excreted into the urine was 35% smaller in subjects with the CES1 c.428G/A genotype than in those with the c.428G/G genotype (P = 0.044). The CES1 genotype had no significant effect on the enalaprilat to enalapril AUC0–∞ ratio or on any other pharmacokinetic or pharmacodynamic parameters of enalapril or enalaprilat. The CES1 genotype had no significant effect on the pharmacokinetic or pharmacodynamic parameters of quinapril.Conclusions
The CES1 c.428G > A SNV decreased enalaprilat concentrations, probably by reducing the hydrolysis of enalapril, but had no observable effect on the pharmacokinetics of quinapril. 相似文献72.
Janne Hukkanen Johanna Puurunen Tuulia Hy?tyl?inen Markku J Savolainen Aimo Ruokonen Laure Morin-Papunen Matej Ore?i? Terhi Piltonen Juha S Tapanainen 《British journal of clinical pharmacology》2015,80(3):473-479
Aims
Atorvastatin is known to both inhibit and induce the cytochrome P450 3A4 (CYP3A4) enzyme in vitro. Some clinical studies indicate that atorvastatin inhibits CYP3A4 but there are no well-controlled longer term studies that could evaluate the inducing effect of atorvastatin. We aimed to determine if atorvastatin induces or inhibits CYP3A4 activity as measured by the 4β-hydroxycholesterol to cholesterol ratio (4βHC : C).Methods
In this randomized, double-blind, placebo-controlled 6 month study we evaluated the effects of atorvastatin 20 mg day−1 (n = 15) and placebo (n = 14) on oxysterol concentrations and determined if atorvastatin induces or inhibits CYP3A4 activity as assessed by the 4βHC : C index. The respective 25-hydroxycholesterol and 5α,6α-epoxycholesterol ratios were used as negative controls.Results
Treatment with atorvastatin decreased 4βHC and 5α,6α-epoxycholesterol concentrations by 40% and 23%, respectively. The mean 4βHC : C ratio decreased by 13% (0.214 ± 0.04 to 0.182 ± 0.04, P = 0.024, 95% confidence interval (CI) of the difference –0.0595, –0.00483) in the atorvastatin group while no significant change occurred in the placebo group. The difference in change of 4βHC : C between study arms was statistically significant (atorvastatin –0.032, placebo 0.0055, P = 0.020, 95% CI of the difference –0.069, –0.0067). The ratios of 25-hydroxycholesterol and 5α,6α-epoxycholesterol to cholesterol did not change.Conclusions
The results establish atorvastatin as an inhibitor of CYP3A4 activity. Furthermore, 4βHC : C is a useful index of CYP3A4 activity, including the conditions with altered cholesterol concentrations. 相似文献73.
74.
75.
Chipanta David Pettifor Audrey Edwards Jessie Giovenco Danielle Topazian Hillary Mariko Bray Rachel M. Millington Monique C. Estill Janne Keiser Olivia Justman Jessica E. 《AIDS and behavior》2022,26(9):3068-3078
AIDS and Behavior - We aimed to measure social protection coverage among the general population, women and men living with HIV (WLHIV, MLHV), female and male sex workers (FSW, MSW), men who have... 相似文献
76.
Diagnostic value of ascitic fluid cholesterol levels in the prediction of malignancy 总被引:1,自引:0,他引:1
P B Mortensen S D Kristensen A Bloch B A Jacobsen S N Rasmussen 《Scandinavian journal of gastroenterology》1988,23(9):1085-1088
In a prospective study abdominal paracentesis with ascitic fluid aspiration was performed in 54 consecutive patients with ascites of unknown cause. The ascitic fluid was examined cytologically and bacteriologically. The total cholesterol concentration was measured with an enzymatic colorimetric method. Malignant disease was diagnosed in 34 patients. Two of them had both malignant disease and liver cirrhosis and were excluded. Seventeen patients had liver cirrhosis, one had acute pancreatitis, and two had decompensated heart disease. The diagnostic value of an ascitic cholesterol concentration greater than 1.2 mmol/l in terms of predicting malignant disease was 87.5% (95% confidence limits, 71.0-96.5). The predictive value of an ascitic cholesterol concentration less than or equal to 1.2 mmol/l in terms of benign disease was 80.0% (95% confidence limits, 56.3-94.3). It is concluded that ascitic cholesterol measurement is a valuable supplement to cytologic examination in distinguishing between ascites of malignant and benign origin. 相似文献
77.
The surgical management of perianal Crohn's disease is complex with a wide range of operations being described. The initial emergency treatment is to drain any source of underlying sepsis. A loose seton drainage or a defunctioning stoma can then be used as a 'bridge' to definitive treatment allowing both adequate assessment of the condition and preventing further sepsis. The likelihood of success of any surgical repair must be weighed against the risk of faecal incontinence. Improved results of a local surgical repair are seen with optimal surgical and medical management of perianal Crohn's disease. 相似文献
78.
Hawkey C Laine L Simon T Beaulieu A Maldonado-Cocco J Acevedo E Shahane A Quan H Bolognese J Mortensen E 《Arthritis and rheumatism》2000,43(2):370-377
OBJECTIVE: This randomized, double-blind study tested the hypothesis that rofecoxib, a drug that specifically inhibits cyclooxygenase 2, would cause fewer gastroduodenal ulcers than ibuprofen (in a multicenter trial), and its side effects would be equivalent to those of placebo (in a prespecified analysis combining the results with another trial of identical design). METHODS: Seven hundred seventy-five patients with osteoarthritis were randomized to receive rofecoxib at a dosage of 25 mg or 50 mg once daily, ibuprofen 800 mg 3 times daily, or placebo. Gastroduodenal ulceration was assessed by endoscopy at 6, 12, and (for active treatment) 24 weeks. The primary and secondary end points were the incidence of gastroduodenal ulcers at 12 and 24 weeks, respectively. RESULTS: Ulcers were significantly less common (P < 0.001) following treatment with rofecoxib (25 mg or 50 mg) than with ibuprofen after 12 weeks (5.3% and 8.8% versus 29.2%, respectively) or 24 weeks (9.9% and 12.4% versus 46.8%, respectively). In the combined analysis, the 12-week ulcer incidence with 25 mg rofecoxib (4.7%) and with placebo (7.3%) satisfied prespecified criteria for equivalence. CONCLUSION: At 2-4 times the therapeutically effective dose, rofecoxib caused fewer endoscopically detected ulcers than did ibuprofen. Rofecoxib at a dose of 25 mg (the highest dose recommended for osteoarthritis) satisfied prespecified criteria for equivalence to placebo. 相似文献
79.
Nerve mediated relaxation of the human internal anal sphincter: the role of nitric oxide. 总被引:18,自引:4,他引:18
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The aim of this study was to determine if nitric oxide (NO) is the non-adrenergic, non-cholinergic neurotransmitter, released by enteric inhibitory nerves, which mediates relaxation of the human internal anal sphincter. Isolated muscle strips were mounted for isometric tension recording in superfusion organ baths. Sodium nitroprusside, an exogenous donor of NO, relaxed the strips in a concentration dependent manner. In the presence of atropine and guanethidine, transmural field stimulation produced tetrodotoxin sensitive relaxations, which were inhibited in a dose dependent and enantiomer specific manner by antagonists of NO synthase; completely by L-nitroarginine and partially by L-N-monomethyl arginine. The effect of these antagonists was reversed by L-arginine but not D-arginine. Oxyhaemoglobin, a scavenger of nitric oxide, also abolished the relaxations but methaemoglobin had no such effect. These results strongly suggest that NO is, or is very closely associated with, the non-adrenergic, non-cholinergic neurotransmitter mediating neurogenic relaxation of the human internal anal sphincter. 相似文献
80.
Diagnosis of Helicobacter pylori in bleeding peptic ulcer patients,evaluation of urea-based tests 总被引:1,自引:0,他引:1
Wildner-Christensen M Touborg Lassen A Lindebjerg J Schaffalitzky de Muckadell OB 《Digestion》2002,66(1):9-13
BACKGROUND/AIMS: The prevalence of Helicobacter pylori (Hp) has been reported to be lower in patients with bleeding peptic ulcers than in patients with nonbleeding peptic ulcers. This might be due to inaccuracy of the urease-based diagnostic tests when used in patients with bleeding peptic ulcers. The aims of this study were to compare the validity of the rapid urease test (RUT) and (13)C-urea breath test in patients with bleeding (group 1) and nonbleeding peptic ulcers (group 2) and to examine whether the presence of blood in the stomach influences the validity of urease-based tests. METHODS: 95 consecutive patients with bleeding peptic ulcers (48 with and 47 without blood in the stomach) and 44 with uncomplicated peptic ulcers. Biopsies for RUT and histology were obtained during endoscopy. After endoscopy a (13)C-urea breath test was performed. Positive histology was used as 'gold standard' defining positive Hp-status. RESULTS: The prevalence of Hp-infection was 44/95 (46%) in group 1 and 29/44 (66%) in group 2 (p = 0.04). The sensitivities and specificities of RUT, (13)C-urea breath test and serology (control) were between 0.72 and 0.96; no difference was found between the groups. In group 1 the sensitivity of the RUT decreased from 0.96 when no blood was present to 0.60 when blood was present (p = 0.006). The sensitivity of (13)C-urea breath test was not affected by blood in the stomach. CONCLUSION: When comparing patients with bleeding and nonbleeding peptic ulcers, we did not find any difference in either sensitivity or specificity of the diagnostic tests for Hp. However, the sensitivity of the RUT was lower when blood was present in the stomach, which was the case in only half of the patients. The sensitivity and specificity of the (13)C-urea breath test was not affected by the presence of blood in the stomach. 相似文献