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Joshua Sampson Kevin Jacobs Meredith Yeager Stephen Chanock Nilanjan Chatterjee 《Genetic epidemiology》2011,35(4):269-277
Next Generation Sequencing represents a powerful tool for detecting genetic variation associated with human disease. Because of the high cost of this technology, it is critical that we develop efficient study designs that consider the trade‐off between the number of subjects (n) and the coverage depth (µ). How we divide our resources between the two can greatly impact study success, particularly in pilot studies. We propose a strategy for selecting the optimal combination of n and µ for studies aimed at detecting rare variants and for studies aimed at detecting associations between rare or uncommon variants and disease. For detecting rare variants, we find the optimal coverage depth to be between 2 and 8 reads when using the likelihood ratio test. For association studies, we find the strategy of sequencing all available subjects to be preferable. In deriving these combinations, we provide a detailed analysis describing the distribution of depth across a genome and the depth needed to identify a minor allele in an individual. The optimal coverage depth depends on the aims of the study, and the chosen depth can have a large impact on study success. Genet. Epidemiol. 35: 269‐277, 2011. © 2011 Wiley‐Liss, Inc. 相似文献
994.
Neuropsychological Deficits in Adolescents with Fetal Alcohol Syndrome: Clinical Findings 总被引:10,自引:0,他引:10
Heather Carmichael Olson Julie J. Feldman Ann P. Streissguth Paul D. Sampson Fred L. Bookstein 《Alcoholism, clinical and experimental research》1998,22(9):1998-2012
Understanding the nature of cognitive deficits among adolescent patients with fetal alcohol syndrome (FAS) can direct future research on assessment and intervention. In an exploratory study, nine non-retarded teenagers with FAS were administered tests of IQ and adaptive behavior, and neuropsychological tests presumed sensitive to alcohol effects. Their performance was compared with psychometric norms and to data from a sample of 174 adolescents with minimal or no prenatal alcohol exposure. These nonretarded FAS patients commonly showed behavior problems, decreased social competence, and poor school performance. Neuropsychological testing revealed significant deficits, although no one neuropsychological profile characterized all patients and not all tests revealed problems. Relatively intact performance was observed in procedural memory, some measures of reaction time, and some reading measures. Deficits were seen on attentional and memory tasks tapping visual-spatial skills, short-term auditory attention and memory, declarative learning, and cognitive flexibility and planning. Difficulties in processing speed and accuracy were also seen. Comparison with a subgroup of 52 nonalcohol-exposed or minimally alcohol-exposed adolescents with a similar range of IQ scores demonstrated that deficits among these FAS patients were not fully explained by a general lowering of IQ. 相似文献
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996.
A Fetal Alcohol Behavior Scale 总被引:2,自引:0,他引:2
Ann P. Streissguth Fred L. Bookstein Helen M. Barr Shoshanna Press Paul D. Sampson 《Alcoholism, clinical and experimental research》1998,22(2):325-333
This research aimed to develop a Fetal Alcohol Behavior Scale (FABS) that describes the behavioral essence of fetal alcohol syndrome (FAS) and fetal alcohol effects (FAE), regardless of age, race, sex, and IQ. Using a reference sample of 472 diagnosed patients with FAS or FAE, ages 2 to 51, five studies are described. The FABS demonstrates high item-to-scale reliability (Cronbach's α = 0.91) and good test-retest reliability ( r = 0.69) over an average interval of 5 years. It identifies many of the subjects with known or presumed prenatal alcohol exposure in detection studies using both prison and general samples. FABS scores also predict dependent living among adult patients with FAS/FAE. The FABS is uncorrelated with IQ, sex, age, race, and diagnosis (FAS versus FAE). We outline areas of further work to define the specificity and utility of this FABS. 相似文献
997.
Left ventricular diastolic function was assessed by pulsed Doppler echocardiography in non-diabetic controls (n = 11) and in patients with type 1 diabetes without microvascular disease (n = 16; diabetic controls), with microalbuminuria (n = 9), or with early persistent proteinuria (n = 11). The peak filling velocities during the early and atrial phases of left ventricular diastole and their ratio (E:A ratio) were measured. All patients with diabetes had a normal serum concentration of creatinine and exercise electrocardiogram. The mean E:A ratio was significantly lower in those with proteinuria than in the diabetic controls because of an increase in peak atrial filling velocity; most patients with proteinuria had an abnormal E:A ratio of less than 1.0. Multiple regression analysis showed that systolic blood pressure was the major determinant of both the peak filling velocity during the atrial phase of diastole and also left ventricular mass. Blood pressures were significantly higher in the proteinuria group than in the diabetic controls. Glycaemic control and autonomic function did not influence diastolic filling. The slightly raised blood pressures at the earliest stages of diabetic nephropathy are sufficient to alter left ventricular diastolic compliance--this may reflect early hypertensive heart disease. These data do not preclude a specific heart muscle disease related to diabetes, but suggest that these slightly raised blood pressures contribute significantly to left ventricular dysfunction in these patients, in whom the risk of cardiovascular disease is already greatly increased. 相似文献
998.
Ann P. Streissguth Helen M. Barr Heather Carrnichael Olson Paul D. Sampson Fred L. Bookstein Donna M. Burgess 《Alcoholism, clinical and experimental research》1994,18(2):248-254
Women (1529) were interviewed in midpregnancy, and a cohort of their children has been examined at various ages. The two standardized tests presented herein are part of a large battery of tests administered when the children were 14 years old. "Word Attack" ( n =462) measures phonological processing on a task involving the reading of pseudowords in nontimed performance. "Arithmetic" ( n =191) measures auditorily processed mental computations in timed performance. Scores on both tests were associated with prenatal alcohol exposure in a dose-dependent fashion. These effects were robust when considered in relation to a wide variety of potentially confounding variables, such as prenatal exposure to tobacco and other drugs, sociodemographic characteristics, and traumatic postnatal events. A variety of alcohol scores were related to these two performance measures, but those involving a massing of drinks on a given occasion had the strongest association. The higher the average number of drinks/occasion, the poorer the offspring performance on tasks thought to underlie numerical problem solving and reading proficiency. Earlier reports of prenatal, alcohol-related neurobehavioral deficits in childhood have now been extended into adolescence. 相似文献
999.
T B Barrett P Sampson G K Owens S M Schwartz E P Benditt 《Proceedings of the National Academy of Sciences of the United States of America》1983,80(3):882-885
Although polyploid nuclei have long been known to be present in many adult human tissues, the ploidy of smooth muscle cells in human artery wall has never been determined. We measured DNA content in individual smooth muscle cell nuclei of artery wall specimens by two means: Feulgen microdensitometry and flow microfluorimetry. A significant percentage of nuclei were polyploid; most of these were tetraploid, although higher levels were also found. The frequency of polyploidy varied with age from less than 1% at birth to a mean of 7% in adult aortic, carotid, and iliac vessels. Atherosclerotic plaques had a lower tetraploid content than the underlying media, whereas normal intima was similar to the corresponding media. The increase in frequency of hyperploid smooth muscle cell nuclei correlates with the normal growth, development, and aging of human artery wall. We suggest that the regular existence of a subset of polyploid smooth muscle cells may indicate an important functional role for this phenotype. 相似文献
1000.
Hogan HA Argueta F Moe L Nguyen LP Sampson HW 《Alcoholism, clinical and experimental research》2001,25(5):746-754
BACKGROUND: Alcohol is a known risk factor for osteopenia and fracture in humans, and its effects on the skeleton have been studied extensively in animal models. Almost all studies of rats, however, have begun rats on alcohol diets while the animals were young and still growing. The purpose of the current study was to examine the effects of alcohol consumption on rats that began drinking alcohol as adults, so that the confounding effects of growth might be minimized. METHODS: Nine-month-old female Sprague-Dawley rats were studied for two durations (8 and 14 weeks). The following diet groups were used for both durations: alcohol (n = 7), in which rats were fed a liquid diet containing ethanol (8.1% v/v; Lieber-DeCarli method); pair-fed (n = 7), in which rats were fed a caloric-equivalent liquid diet matched to the alcohol-fed animals; and pellet (n = 6), in which rats consumed standard rat chow and water. A cessation protocol was also used in which alcohol- and pair-fed groups were fed liquid diets for 8 weeks and then given pellet chow and water for 6 weeks, with pair feeding maintained during the cessation period. RESULTS: Only minor effects developed in the rats in the 8-week group, but after 14 weeks, the cancellous bone of the proximal tibia was severely osteopenic in the alcohol-fed animals. The bone volume and trabecular number were both significantly lower in the alcohol-fed animals than in the pair-fed and pellet-fed control animals and also lower than in the alcohol-fed animals in the 8-week group. Mechanical properties of the cancellous bone in the distal femur also were significantly diminished in the 14-week alcohol-fed group. Composition and mechanical properties of the cortical bone in the femur diaphysis were largely unaffected, but the yield stress was significantly lower in the 14-week alcohol-fed group than in the 8-week alcohol-fed group. No significant effects were found in the cessation groups with regard to almost all parameters measured. CONCLUSIONS: Our study results demonstrate that chronic adult-onset alcohol consumption leads to significantly diminished cancellous bone properties and that these effects depend on the duration of alcohol use. 相似文献