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111.
Multicenter linkage study of schizophrenia candidate regions on chromosomes 5q, 6q, 10p, and 13q: schizophrenia linkage collaborative group III 总被引:7,自引:0,他引:7 下载免费PDF全文
Levinson DF Holmans P Straub RE Owen MJ Wildenauer DB Gejman PV Pulver AE Laurent C Kendler KS Walsh D Norton N Williams NM Schwab SG Lerer B Mowry BJ Sanders AR Antonarakis SE Blouin JL DeLeuze JF Mallet J 《American journal of human genetics》2000,67(3):652-663
Schizophrenia candidate regions 33-51 cM in length on chromosomes 5q, 6q, 10p, and 13q were investigated for genetic linkage with mapped markers with an average spacing of 5.64 cM. We studied 734 informative multiplex pedigrees (824 independent affected sibling pairs [ASPs], or 1,003 ASPs when all possible pairs are counted), which were collected in eight centers. Cases with diagnoses of schizophrenia or schizoaffective disorder (DSM-IIIR criteria) were considered affected (n=1,937). Data were analyzed with multipoint methods, including nonparametric linkage (NPL), ASP analysis using the possible-triangle method, and logistic-regression analysis of identity-by-descent (IBD) sharing in ASPs with sample as a covariate, in a test for intersample heterogeneity and for linkage with allowance for intersample heterogeneity. The data most supportive for linkage to schizophrenia were from chromosome 6q; logistic-regression analysis of linkage allowing for intersample heterogeneity produced an empirical P value <.0002 with, or P=.0004 without, inclusion of the sample that produced the first positive report in this region; the maximum NPL score in this region was 2.47 (P=.0046), the maximum LOD score (MLS) from ASP analysis was 3.10 (empirical P=.0036), and there was significant evidence for intersample heterogeneity (empirical P=.0038). More-modest support for linkage was observed for chromosome 10p, with logistic-regression analysis of linkage producing an empirical P=. 045 and with significant evidence for intersample heterogeneity (empirical P=.0096). 相似文献
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Ewen KR Bahlo M Treloar SA Levinson DF Mowry B Barlow JW Foote SJ 《American journal of human genetics》2000,67(3):727-736
Although it is clear that errors in genotyping data can lead to severe errors in linkage analysis, there is as yet no consensus strategy for identification of genotyping errors. Strategies include comparison of duplicate samples, independent calling of alleles, and Mendelian-inheritance-error checking. This study aimed to develop a better understanding of error types associated with microsatellite genotyping, as a first step toward development of a rational error-detection strategy. Two microsatellite marker sets (a commercial genomewide set and a custom-designed fine-resolution mapping set) were used to generate 118,420 and 22,500 initial genotypes and 10,088 and 8,328 duplicates, respectively. Mendelian-inheritance errors were identified by PedManager software, and concordance was determined for the duplicate samples. Concordance checking identifies only human errors, whereas Mendelian-inheritance-error checking is capable of detection of additional errors, such as mutations and null alleles. Neither strategy is able to detect all errors. Inheritance checking of the commercial marker data identified that the results contained 0.13% human errors and 0.12% other errors (0.25% total error), whereas concordance checking found 0.16% human errors. Similarly, Mendelian-inheritance-error checking of the custom-set data identified 1.37% errors, compared with 2.38% human errors identified by concordance checking. A greater variety of error types were detected by Mendelian-inheritance-error checking than by duplication of samples or by independent reanalysis of gels. These data suggest that Mendelian-inheritance-error checking is a worthwhile strategy for both types of genotyping data, whereas fine-mapping studies benefit more from concordance checking than do studies using commercial marker data. Maximization of error identification increases the likelihood of linkage when complex diseases are analyzed. 相似文献
113.
George C. Griffith Richard S. Cosby David C. Levinson 《The Western journal of medicine》1950,72(6):431-441
The diagnosis of uncomplicated ventricular septal defect and uncomplicated patent ductus arteriosus presents few hazards. Differential diagnosis of atrial septal defect and of transposed pulmonary veins is technically more difficult. The complex nature of most types of cyanotic congenital heart disease requires the combined use of catheterization, determination of circulation times, ventilation studies, and possibly angiocardiography.Reports of eight cases in which cardiac catheterization was carried out illustrate the common forms of acyanotic and cyanotic heart disease and the factors in diagnosis. 相似文献
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Neuraminidase treatment modifies the function of electroplax sodium channels in planar lipid bilayers 总被引:10,自引:0,他引:10
Sodium channels from several sources are covalently modified by unusually large numbers of negatively charged sialic acid residues. In the present studies, purified electroplax sodium channels were treated with neuraminidase to remove sialic acid residues and then examined for functional changes in planar lipid bilayers. Neuraminidase treatment resulted in a large depolarizing shift in the average potential required for channel activation. Additionally, desialidated channels showed a striking increase in the frequency of reversible transitions to subconductance states. Thus it appears that sialic acid residues play a significant role in the function of sodium channels, possibly through their influence on the local electric field and/or conformational stability of the channel molecule. 相似文献
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Inhibition of RNA slow viruses by thiosemicarbazones 总被引:8,自引:0,他引:8
120.
In conversation, negative responses to invitations, requests, offers, and the like are more likely to occur with a delay–conversation analysts talk of them as dispreferred. Here we examine the contrastive cognitive load ‘yes’ and ‘no’ responses make, either when relatively fast (300 ms after question offset) or delayed (1000 ms). Participants heard short dialogues contrasting in speed and valence of response while having their EEG recorded. We found that a fast ‘no’ evokes an N400-effect relative to a fast ‘yes’; however, this contrast disappeared in the delayed responses. ''No'' responses, however, elicited a late frontal positivity both if they were fast and if they were delayed. We interpret these results as follows: a fast ‘no’ evoked an N400 because an immediate response is expected to be positive–this effect disappears as the response time lengthens because now in ordinary conversation the probability of a ‘no’ has increased. However, regardless of the latency of response, a ‘no’ response is associated with a late positivity, since a negative response is always dispreferred. Together these results show that negative responses to social actions exact a higher cognitive load, but especially when least expected, in immediate response. 相似文献