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M A Bernhisel J F Holman A F Haney D W Schomberg 《The Journal of clinical endocrinology and metabolism》1987,64(6):1251-1256
The role(s) of androgens in the steroidogenic regulation of human granulosa cell production of estrogen and progesterone during monolayer culture was studied. These cells were exposed in vivo to human menopausal gonadotropin and hCG gonadotropin with or without clomiphene citrate. Steroid production rates were compared between cells cultured in control medium and those cultured in medium containing a nonaromatizable androgen [dihydrotestosterone (DHT)] or an aromatizable androgen [androstenedione (A'D)]. Some cultures received A'D from 3-12 days; other cultures received DHT alone for 3, 6, or 9 days before the addition of A'D for 3 days. The effect on steroid production during the culture interval before the addition of A'D also was evaluated. Exposure to A'D increased estrogen production over 50-fold compared with that in control cells or those treated with DHT (P less than 0.001). DHT also failed to alter estrogen production when A'D was added to cultures. Furthermore, the delay in introducing A'D to the cultures for up to 9 days did not decrease subsequent estrogen production compared with that in cultures continually exposed to A'D or DHT plus A'D. Progesterone production was substantial for at least 12 days of culture and was unaffected by the presence of androgen. These results do not confirm previous studies using murine or porcine granulosa cells, which suggested that androgen receptor-dependent mechanisms were involved in increasing estrogen and/or progesterone production in vitro. Rather, they indicate that androgen may not be required to maintain aromatase capability per se in human granulosa-luteal cells previously exposed to ovulation-inducing quantities of gonadotropin. 相似文献
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Population-based epidemiology of human immunodeficiency virus infection in Western Australia. Western Australian AIDS Advisory Committee 总被引:2,自引:0,他引:2
C D Holman P V Cameron M R Bucens A J Keller J Machin J C McNulty 《The Medical journal of Australia》1989,150(7):362-4, 367, 370
A total of 328 cases of infection with human immunodeficiency virus (HIV) in Western Australia in 1983-1987 was studied with respect to demographic factors, the risk profile, the clinical progression of disease, the utilization of inpatient services and trends in incidence over time. The crude incidence rates were 8.8 cases/100,000 person-years in men and 0.4 cases/100,000 person-years in women. Age-specific rates peaked at 25 to 29 years of age in men. The risk of HIV infection was associated with metropolitan residence, low socioeconomic level, and two specific occupational groups. Homosexual and bisexual men constituted 86% of all cases; the incidence rate of HIV infection in such men was approximately 1000-times higher than was the incidence rate by apparent sexual transmission in heterosexual persons. However, the proportion of cases that occurred in women or that apparently was caused by heterosexual sexual transmission increased from zero in 1983-1984 to 7.5% and 5.4%, respectively, in 1987. After two years of follow-up, 71% of preclinical (category-C) patients had developed signs, symptoms or evidence of immune dysfunction, and 12% of those patients with lymphadenopathy or with other early clinical features of disease (category-B) had progressed to the acquired immunodeficiency syndrome (AIDS). At 21 months of follow-up, the survival rate with AIDS was 9%. Patients with AIDS utilized an average of 68.9 short-stay hospital bed-days per person-year, while category-B patients used 11.5 hospital bed-days per person-year. Notifications of HIV infection increased each year from 1983 to 1986, but fell by 22% in 1987. The latter may have been as a result of chance, a screening artefact or a real reduction in the incidence rate. 相似文献
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AIMS: To determine the most appropriate regression models to use when assessing risk factors for severe hypoglycaemia and to investigate the impact of model misspecification and its clinical implications. METHODS: A total of 1229 children with Type 1 diabetes (mean age 11.7 years sd 4.1), of which 605 (49.2%) were males, were studied. Prospective assessment of severe hypoglycaemia (an event leading to loss of consciousness or seizure) was made over the 9-year period, 1992-2001. Patients were seen every 3 months and episodes of hypoglycaemia along with clinical data were recorded. Over 70% of children never experienced a severe hypoglycaemic event. Data were analysed using the Poisson regression, negative binomial, zero-inflated Poisson (ZIP) and zero-inflated negative binomial (ZINB) models. The over-dispersion and likelihood ratio statistics were calculated and the analytical methods compared. RESULTS: The Poisson regression model did not fit the data well. The negative binomial and the zero inflated Poisson and negative binomial models fitted the data better than Poisson. CONCLUSIONS: The commonly used Poisson regression models to analyse hypoglycaemia epidemiology may lead to biased parameter estimates and incorrect determination of risk factors for hypoglycaemia. We recommend the use of the negative binomial or zero inflated models to examine any risk factors associated with severe hypoglycaemia. Careful consideration must be given to the interpretation of hypoglycaemia surveys and their analysis. 相似文献
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Ronald B. George Abigail H. Melnick Erin C. Rose Ashraf S. Habib 《Journal canadien d'anesthésie》2007,54(3):218-222
PURPOSE: To report the use of regional anesthesia and iv nitroglycerin to provide anesthesia and uterine relaxation for three Cesarean deliveries (CD) involving ex utero intrapartum treatment (EXIT) of potentially life-threatening airway obstruction in the newborn. CLINICAL FEATURES: Case 1--a 36-yr-old woman at 38 weeks' gestation was scheduled for an elective CD for fetal skeletal dysplasia and micrognathia. Case 2--a 34-yr-old woman at 35 weeks gestation had a fetal ultrasound revealing fixed neck flexion and micrognathia consistent with fetal arthrogryposis. Case 3--a 27-yr-old woman presented at 38 weeks gestation for CD for severe fetal micrognathia, with mandibular growth below the fifth percentile. For each case, a combined spinal epidural anesthetic was performed with 0.75% bupivacaine, fentanyl and morphine intrathecally followed by placement of a multiorifice epidural catheter. Prior to uterine incision patients received a loading dose followed by an iv infusion of nitroglycerin. Uterine relaxation was sufficient in all cases for delivery of the fetus, and allowed for evaluation by direct laryngoscopy and intubation while maintaining fetal-placental circulation. The surgical procedures were completed without incident. CONCLUSIONS: Anesthesia and uterine relaxation for CD and EXIT procedures can be safely provided with regional anesthesia and iv nitroglycerin. 相似文献
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J T Eells P A Bandettini P A Holman J M Propp 《The Journal of pharmacology and experimental therapeutics》1992,262(3):1173-1181
The neuroexcitatory actions of two toxicologically distinct classes of pyrethroid insecticides were characterized in rat brain synaptosomes using [3H]tetraphenylphosphonium to measure changes in synaptosomal membrane potential and by measuring the release of [3H]acetylcholine. Both type I (permethrin) and type II (deltamethrin, cypermethrin and fenvalerate) pyrethroids produced a concentration-dependent tetrodotoxin-sensitive membrane depolarization which was stereospecific for the neurotoxic isomer of each pyrethroid. Deltamethrin was the most potent and efficacious pyrethroid in these studies, with an EC50 of 30 nM and a maximal estimated membrane depolarization of 27 mV, followed by cypermethrin, fenvalerate and permethrin. The phenoxybenzyl pyrethroids also increased the spontaneous release of [3H]acetylcholine from rat brain synaptosomes, further supporting a depolarizing action of these insecticides on nerve terminal membranes. Pyrethroid-induced release of [3H]acetylcholine was tetrodotoxin-sensitive and occurred over the same concentration range as membrane depolarization. These data indicate that type I and type II phenoxybenzyl pyrethroids act potently and stereoselectively on the voltage-sensitive sodium channel to increase sodium influx into synaptic terminals producing membrane depolarization and neurotransmitter release. Furthermore, they show that pyrethroid-induced alterations in synaptosomal membrane potential is a sensitive measure of pyrethroid action on the sodium channel and of pyrethroid toxicity. 相似文献