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21.
Increased carotid atherosclerosis in andropausal middle-aged men 总被引:2,自引:0,他引:2
Mäkinen J Järvisalo MJ Pöllänen P Perheentupa A Irjala K Koskenvuo M Mäkinen J Huhtaniemi I Raitakari OT 《Journal of the American College of Cardiology》2005,45(10):1603-1608
OBJECTIVES: This study examined the association between carotid artery intima-media thickness (IMT), serum sex hormone levels, and andropausal symptoms in middle-aged men. BACKGROUND: Male sex hormones may play a dual role in the pathogenesis of atherosclerosis in men by carrying both proatherogenic and atheroprotective effects. METHODS: We studied 239 40- to 70-year-old men (mean +/- SD: 57 +/- 8 years) who participated in the Turku Aging Male Study and underwent serum lipid and sex hormone measurements. Ninety-nine men (age 58 +/- 7 years) were considered andropausal (i.e., serum testosterone <9.8 nmol/l or luteinizing hormone [LH] >6.0 U/l and testosterone in the normal range), and in both situations, they had subjective symptoms of andropause (a high symptom score in questionnaire). Three were excluded because of diabetes. The rest of the men (age 57 +/- 8 years) served as controls. Carotid IMT was determined using high-resolution B-mode ultrasound, and serum testosterone, estradiol (E2), LH, and sex hormone-binding globulin were measured using standard immunoassays. RESULTS: Andropausal men had a higher maximal IMT compared with controls in the common carotid (1.08 +/- 0.34 vs. 1.00 +/- 0.23, p < 0.05) and in the carotid bulb (1.44 +/- 0.48 vs. 1.27 +/- 0.35, p = 0.003). Common carotid IMT correlated inversely with serum testosterone (p = 0.003) and directly with LH (p = 0.006) in multivariate models adjusted for age, total cholesterol, body mass index, blood pressure, and smoking. CONCLUSIONS: Middle-aged men with symptoms of andropause, together with absolute or compensated (as reflected by high normal to elevated LH) testosterone deficiency, show increased carotid IMT. These data suggest that normal testosterone levels may offer protection against the development of atherosclerosis in middle-aged men. 相似文献
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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25.
Surfactant protein A and B genetic variants in respiratory distress syndrome in singletons and twins 总被引:3,自引:0,他引:3
Marttila R Haataja R Guttentag S Hallman M 《American journal of respiratory and critical care medicine》2003,168(10):1216-1222
Interactive genetic and environmental factors may influence the differentiation of surfactant and the risk of respiratory distress syndrome (RDS). DNA samples from 441 premature singleton infants and 480 twin or multiple infants were genotyped for surfactant-specific protein (SP)-A1, SP-A2, and SP-B exon 4 polymorphisms and intron 4 size variants in a homogeneous white population. Distributions of the SP-A and SP-B gene variants between RDS and no-RDS infants were determined alone and in combination. SP-A1 allele 6A2 (p = 0.009) and the homozygous genotype 6A2/6A2 (p = 0.003) were overrepresented in RDS of singletons when the SP-B exon 4 genotype was Thr/Thr, and underrepresented in RDS of multiples when the SP-B genotype was Ile/Thr (p = 0.012 for 6A2 and p = 0.03 for 6A2/6A2) or Thr/Thr (p = 0.12 for 6A2 and p = 0.018 for 6A2/6A2, respectively). The SP-A 6A2 allele in the SP-B Thr131 background predisposed the smallest singleton infants to RDS, whereas near-term multiples were protected from RDS. There was a continuous association between fetal mass and risk of RDS, defined by the SP-A and SP-B variants. Labeled lung explants with the Thr/Thr genotype showed proSP-B amino-terminal glycosylation, which was absent in Ile/Ile samples. Genetic and environmental variation may influence intracellular processing of surfactant complex and the susceptibility to RDS. 相似文献
26.
Katoh S Lehtovirta M Kaprio J Harjutsalo V Koskenvuo M Eriksson J Tajima N Tuomilehto J 《The Journal of clinical endocrinology and metabolism》2005,90(5):2642-2647
The aim of this study was to evaluate genetic and environmental effects on plasma glucose, insulin secretion, and resistance in Finnish twins. Altogether 151 randomly selected twin pairs were examined by the oral glucose tolerance test; 66 twin pairs were monozygotic and 85 like-sexed dizygotic. We estimated the intraclass correlation coefficients and variance components of genetic and environmental effects on waist circumference, plasma glucose, and serum insulin. For fasting insulin, the proportion of total variation accounted for by additive genetic effects (A) and nonshared environmental effects (E) were 43 and 57%, respectively. As to postchallenge insulin and waist circumference, A effects were stronger in female twins (51 and 70%, respectively) than male twins in whom no significant evidence for genetic variance was found. Of the variation in fasting glucose, A and E effects accounted for 45 and 55%, respectively. Of the variation in postchallenge glucose, E effects had a greater role (65%), compared with A effects (35%); A effects on pre- and postchallenge insulin levels were highly correlated (genetic correlation coefficient = 0.81). In conclusion, additive genetic effects are important for the insulin secretion, whereas nonshared environmental effects contribute strongly to peripheral insulin resistance. 相似文献
27.
BACKGROUND AND AIMS: In a few, earlier, uncontrolled trials, alleviation of chronic pain has been documented by vitamin D supplementation. This randomized double-blind placebo controlled trial addressed the association between pain and vitamin D deficiency and the effects of vitamin D supplementation on pain in institutionalized aged patients. METHODS: 216 long-term care patients were enrolled in Helsinki, Finland. Pain was assessed by three tools: Resident Assessment Instrument (RAI), Discomfort Behavior Scale, and Pain Assessment in Advanced Dementia Scale. Scores for Cognitive Performance Scale (CPS) and other clinical assessments were also collected from the RAI-database. Levels of 25-hydroxyvitamin D (25- OHD) and parathyroid hormone were also determined. Patients in pain (n=202) were randomized into three treatment groups, each receiving 0, 400, or 1200 IU cholecalciferol per day, respectively. Assessments were repeated after six-month vitamin D supplementation. RESULTS: Patients were aged (84.5+/-7.5 yrs), demented (CPS= 4.9+/-1.4, range 1-6), and chronically bedridden. Pain was present in 38.4% to 83.8% of patients depending on assessment tool. Low 25-OHD levels (<50 nmol/L) were very common (98.1%). However, vitamin D deficiency was not associated with pain or pain behavior. The supplementation resulted in a marked increase in 25-OHD levels. However, neither prevalence of painlessness nor pain scores changed significantly after vitamin D supplementation. CONCLUSIONS: We were not able either to show an association between vitamin D deficiency and pain or to observe alleviation of pain by vitamin D supplementation. The independent role of vitamin D in the etiology of pain remains controversial. 相似文献
28.
Niina Onnela Leena Lehtonen Mikko Koski Jari Hyttinen 《Medical & biological engineering & computing》2013,51(1-2):61-70
The purpose of this study is to develop and test a method to reveal if the retinal pigment epithelium (RPE) cells differentiated from human embryonic stem cells (hESC) support the functions of photoreceptors. hESC-derived RPE (hESC–RPE) cells offer a potent cell source for cell replacement therapy that may be used to prevent certain eye diseases. Methods to assure the functionality of the RPE cells are well warranted. Electroretinograms (ERG) measure the electrophysiological response of the retina to light stimuli. A setup was developed that enables the measurement of ERG in vitro from mice retinas cultured together with hESC–RPE cells. The co-culture of RPE and retinas seems to be a viable tool to assess the functionality of RPE in vitro. However, owing to limited sample size results were somewhat mixed, and thus it was not possible to prove that hESC–RPE cells enhance the ERG response of a mouse retina in vitro. The long-term culturing of the retinas needs to be refined to acquire more conclusive evidence of the supporting role of the RPE and to explore the full potential of the co-culture and ERG methods in assessing RPE functionality. 相似文献
29.
Anu Muraja‐Murro Antti Kulkas Mikko Hiltunen Salla Kupari Taina Hukkanen Pekka Tiihonen Esa Mervaala Juha Töyräs 《Journal of sleep research》2013,22(6):663-669
Obstructive sleep apnea (OSA) is linked to an increased mortality rate. However, the severity of individual obstruction events is rarely considered quantitatively in clinical practice. We hypothesized that OSA with especially severe obstruction events would predispose a patient to greater health risks than OSA with a similar apnea–hypopnea index (AHI), but lower severity of individual events. This hypothesis was tested in a follow‐up (198.2 ± 24.7 months) of a population of 1068 men referred for ambulatory polygraphic recording due to suspected OSA. The recordings were analysed according to the guidelines of the American Academy of Sleep Medicine. Furthermore, a novel obstruction severity parameter was determined; this was defined as the product of duration of the individual obstruction event and area of the related desaturation event. Patients treated with continuous positive airway pressure (CPAP) were omitted. We identified 125 deceased patients from our original population and for 113 of these a matching alive patient with similar AHI, age, body mass index (BMI), smoking habits and follow‐up time could be found. The deceased patients with severe OSA (based on conventional AHI) showed higher obstruction severity values than their AHI‐matched alive controls. Based on the multivariate logistic regression analysis, obstruction severity was the only parameter which was related statistically significantly to mortality in the severe OSA category. Furthermore, 59% of all deceased patients and 83% of those who had severe OSA displayed higher obstruction severity than the AHI‐matched alive counterparts. To conclude, the obstruction severity parameter provided valuable prognostic information supplementing AHI. The obstruction severity parameter might improve recognition of the patients with the highest risk. 相似文献
30.
Converting from CT- to MRI-only-based target definition in radiotherapy of localized prostate cancer