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91.
Alcoholism susceptibility loci: confirmation studies in a replicate sample and further mapping 总被引:15,自引:0,他引:15
Foroud T Edenberg HJ Goate A Rice J Flury L Koller DL Bierut LJ Conneally PM Nurnberger JI Bucholz KK Li TK Hesselbrock V Crowe R Schuckit M Porjesz B Begleiter H Reich T 《Alcoholism, clinical and experimental research》2000,24(7):933-945
BACKGROUND: There is substantial evidence for a significant genetic component to the risk for alcoholism. A previous study reported linkage to chromosomes 1, 2, and 7 in a large data set that consisted of 105 families, each with at least three alcoholic members. METHODS: Additional genotyping in the 105 families has been completed in the chromosomal regions identified in the initial analyses, and a replication sample of 157 alcoholic families ascertained under identical criteria has been genotyped. Two hierarchical definitions of alcoholism were employed in the linkage analyses: (1) Individuals who met both Feighner and DSM-III-R criteria for alcohol dependence represented a broad definition of disease; and (2) individuals who met ICD-10 criteria for alcoholism were considered affected under a more severe definition of disease. RESULTS: Genetic analyses of affected sibling pairs supported linkage to chromosome 1 (LOD = 1.6) in the replication data set as well as in a combined analysis of the two samples (LOD = 2.6). Evidence of linkage to chromosome 7 increased in the combined data (LOD = 2.9). The LOD score on chromosome 2 in the initial data set increased after genotyping of additional markers; however, combined analyses of the two data sets resulted in overall lower LOD scores (LOD = 1.8) on chromosome 2. A new finding of linkage to chromosome 3 was identified in the replication data set (LOD = 3.4). CONCLUSIONS: Analyses of a second large sample of alcoholic families provided further evidence of genetic susceptibility loci on chromosomes 1 and 7. Genetic analyses also have identified susceptibility loci on chromosomes 2 and 3 that may act only in one of the two data sets. 相似文献
92.
Gizer IR Edenberg HJ Gilder DA Wilhelmsen KC Ehlers CL 《Alcoholism, clinical and experimental research》2011,35(11):2008-2018
Background: Previous linkage studies, including a study of the Native American population described in the present report, have provided evidence for linkage of alcohol dependence and related traits to chromosome 4q near a cluster of alcohol dehydrogenase (ADH) genes, which encode enzymes of alcohol metabolism. Methods: The present study tested for associations between alcohol dependence and related traits and 22 single‐nucleotide polymorphisms (SNPs) spanning the 7 ADH genes. Participants included 586 adult men and women recruited from 8 contiguous Native American reservations. A structured interview was used to assess DSM‐III‐R alcohol dependence criteria as well as a set of severe alcohol misuse symptoms and alcohol withdrawal symptoms. Results: No evidence for association with the alcohol dependence diagnosis was observed, but an SNP in exon 9 of ADH1B (rs2066702; ADH1B*3) and an SNP at the 5′ end of ADH4 (rs3762894) showed significant evidence of association with the presence of withdrawal symptoms (p = 0.0018 and 0.0012, respectively). Further, a haplotype analysis of these 2 SNPs suggested that the haplotypes containing either of the minor alleles were protective against alcohol withdrawal relative to the ancestral haplotype (p = 0.000006). Conclusions: These results suggest that variants in the ADH1B and ADH4 genes may be protective against the development of some symptoms associated with alcohol dependence. 相似文献
93.
Rice JP Hartz SM Agrawal A Almasy L Bennett S Breslau N Bucholz KK Doheny KF Edenberg HJ Goate AM Hesselbrock V Howells WB Johnson EO Kramer J Krueger RF Kuperman S Laurie C Manolio TA Neuman RJ Nurnberger JI Porjesz B Pugh E Ramos EM Saccone N Saccone S Schuckit M Bierut LJ;the GENEVA Consortium 《Addiction (Abingdon, England)》2012,107(11):2019-2028
AIMS: Nicotine dependence is a highly heritable disorder associated with severe medical morbidity and mortality. Recent meta-analyses have found novel genetic loci associated with cigarettes per day (CPD), a proxy for nicotine dependence. The aim of this paper is to evaluate the importance of phenotype definition (i.e. CPD versus Fagerstr?m Test for Cigarette Dependence (FTCD) score as a measure of nicotine dependence) on genome-wide association studies of nicotine dependence. DESIGN: Genome-wide association study. SETTING: Community sample. PARTICIPANTS: A total of 3365 subjects who had smoked at least one cigarette were selected from the Study of Addiction: Genetics and Environment (SAGE). Of the participants, 2267 were European Americans, 999 were African Americans. MEASUREMENTS: Nicotine dependence defined by FTCD score ≥4, CPD. FINDINGS: The genetic locus most strongly associated with nicotine dependence was rs1451240 on chromosome 8 in the region of CHRNB3 [odds ratio (OR)?=?0.65, P?=?2.4?×?10(-8) ]. This association was further strengthened in a meta-analysis with a previously published data set (combined P?=?6.7?×?10(-16) , total n?=?4200). When CPD was used as an alternate phenotype, the association no longer reached genome-wide significance (β?=?-0.08, P?=?0.0004). CONCLUSIONS: Daily cigarette consumption and the Fagerstrom Test for Cigarette Dependence show different associations with polymorphisms in genetic loci. 相似文献
94.
Schuening FG; Appelbaum FR; Deeg HJ; Sullivan-Pepe M; Graham TC; Hackman R; Zsebo KM; Storb R 《Blood》1993,81(1):20-26
The effects of recombinant canine stem cell factor (rcSCF) on hematopoiesis were studied in normal dogs and in dogs given otherwise lethal total body irradiation (TBI) without marrow transplant. Results were compared with previous and concurrent data with recombinant granulocyte colony-stimulating factor (rG-CSF). Four normal dogs received 200 micrograms rcSCF per kilogram body weight daily either by continuous intravenous infusion for 28 days (n = 2) or by subcutaneous (SC) injection in two divided doses for 20 days (n = 2). All dogs showed at least a twofold increase in peripheral blood neutrophil counts starting approximately 7 days after the initiation of treatment. Hematocrit level and monocyte, lymphocyte, eosinophil, reticulocyte, and platelet counts were not elevated. Marrow sections after rcSCF treatment showed panhyperplasia. The only toxicity was facial edema during the first few days of rcSCF administration, presumably caused by mast cell stimulation. Ten dogs were given 400 cGy TBI at 10 cGy/min from two opposing 60Co sources. They were given no marrow infusion and received 200 micrograms/kg/d rcSCF SC in two divided doses for 21 days starting within 2 hours of TBI. Five of the 10 dogs showed complete and sustained hematopoietic recovery and survived as compared with 1 of 28 control dogs not receiving growth factor (P < .005). RcSCF treatment allowed for hematopoietic recovery in two of seven dogs administered 500 cGy of TBI but in none of five dogs given 600 cGy of TBI. Results with rcSCF are similar to those obtained with rG-CSF. The rate of neutrophil recovery in rcSCF-treated dogs after 400 cGy TBI was not different from that of rG-CSF-treated dogs (P = .65), but the rate of platelet recovery was faster (P = .06) in the rcSCF-treated animals. Combined treatment with rcSCF and rcG-CSF after 500 cGy TBI did not result in strongly improved survival as compared with results obtained with either factor alone. 相似文献
95.
Heterogeneity of breakpoints of 11q23 rearrangements in hematologic malignancies identified with fluorescence in situ hybridization 总被引:3,自引:0,他引:3
Kobayashi H; Espinosa R d; Thirman MJ; Gill HJ; Fernald AA; Diaz MO; Le Beau MM; Rowley JD 《Blood》1993,82(2):547-551
Twenty-four patients whose cells contained a variety of 11q23 rearrangements, including translocations, insertions, and an inversion, were studied using fluorescence in situ hybridization with cosmid, phage, and plasmid probes mapped to 11q22-24. In 17 patients, the breakpoints of the common 11q23 translocations involving chromosomes 4, 6, 9, and 19 as well as some uncommon translocations involving 3q23, 17q25, 10p11, and an insertion 10;11 were all located in the breakpoint cluster region of the MLL gene, regardless of age, phenotype of disease, or involvement of a third chromosome. The breakpoints in 11q23 in the other 7 patients with a t(7;11)(p15;q23), inv(11)(p11q23), t(4;11)(q23;q23), der(5)t(5;11)(q13;q23), ins(10;11)(p11;q23q24), t(11;14)(q23;q11), or t(11;18;11) (p15;q21;q23) were located either centromeric to CD3D or telomeric to THY1. Thus, although most 11q23 rearrangements, involve the same breakpoint cluster region of MLL, there is heterogeneity in the breakpoint in some of the rare rearrangements. 相似文献
96.
97.
98.
A Family-Based Analysis of the Association of the Dopamine D2 Receptor (DRD2) with Alcoholism 总被引:7,自引:0,他引:7
Howard J. Edenberg Tatiana Foroud Daniel L. Koller Alison Goate John Rice Paul Van Eerdewegh Theodore Reich C. Robert Cloninger John I. Nurnberger Jr Maria Kowalczuk Bo Wu T.-K. Li P. M. Conneally Jay A. Tischfield William Wu Shantia Shears Raymond Crowe Victor Hesselbrock Marc Schuckit Bernice Porjesz Henri Begleiter 《Alcoholism, clinical and experimental research》1998,22(2):505-512
The possible association of the DRD2 locus, and in particular the 7aql-A1 allele, with alcoholism remains controversial, in part because of differences in allele frequencies among populations. To avoid problems associated with differences in allele frequencies in different populations, we tested whether the DRD2 locus is associated with alcohol dependence in a large family-based sample. Neither the transmission/disequilibrium test nor the Affected Family-Based Controls test provide any evidence of linkage or association between the DRD2 locus and alcohol dependence. 相似文献
99.
Amani Mubarak Eric Spierings Victorien M Wolters Henny G Otten Fiebo JW ten Kate Roderick HJ Houwen 《World journal of gastroenterology : WJG》2013,19(41):7114-7120
AIM:To investigate whether celiac disease(CD)patients with tissue-transglutaminase antibody(tTGA)≥100 U/mL are different from patients with lower tTGA levels.METHODS:Biopsy-proven(MarshⅢ)pediatric CD patients(n=116)were prospectively included between March 2009 and October 2012.The biopsies were evaluated by a single pathologist who was blinded to all of the patients’clinical data.The patients were distributed into 2 groups according to their tTGA level,which was measured using enzyme-linked immunoassay:tTGA≥100 U/mL and Ttga<100 U/mL.The patients’characteristics,symptoms,human leukocyte antigen(HLA)genotype and degree of histological involvement were compared between the 2 groups.RESULTS:A total of 34(29.3%)children had tTGA values<100 U/mL and 82(70.7%)tTGA levels of≥100 U/mL.Patients with high tTGA levels had lower average body weight-for-height standard deviation scores(SDS)than did patients with tTGA<100 U/mL(-0.20±1.19 SDS vs 0.23±1.03 SDS,P=0.025).In the low tTGA group,gastrointestinal symptoms were more common(97.1%vs 75.6%,P=0.006).More specifically,abdominal pain(76.5%vs 51.2%;P=0.012)and nausea(17.6%vs 3.7%,P=0.018)were more frequent among patients with low tTGA.In contrast,patients with solely extraintestinal manifestations were only present in the high tTGA group(18.3%,P=0.005).These patients more commonly presented with aphthous stomatitis(15.9%vs 0.0%,P=0.010)and anemia(32.9%vs 11.8%,P=0.019).In addition,when evaluating the number of CD-associated HLA-DQ heterodimers(HLA-DQ2.5,HLA-DQ2.2 and HLA-DQ8),patients with low tTGA levels more commonly had only1 disease-associated heterodimer(61.8%vs 31.7%,P=0.005),while patients with high tTGA more commonly had multiple heterodimers.Finally,patients with tTGA≥100 U/mL more often had a MarshⅢc lesion(73.2%vs 20.6%,P≤0.001)while in patients with low tTGA patchy lesions were more common(42.4%vs6.8%,P≤0.001).CONCLUSION:Patients with tTGA≥100 U/mL show several signs of more advanced disease.They also carry a larger number of CD 相似文献
100.
AIM: To demonstrate the range of applying laser angioplasty after unsuccessful recanalization of the superficial femoral artery (SFA) with conventional interventional techniques. MATERIALS AND METHODS: In a prospective trial in 94 cases with occlusion of the SFA and formerly unsuccessful conventional percutaneous transluminal angioplasty, laser angioplasty for recanalization was applied. The average length of the SFA was 17.5 cm (range 4–36 cm). The recanalization attempt was made using the crossover technique in 78 patients, in eight patients with the antegrade technique and in another eight patients using the transpopliteal technique. The primary recanalization attempt was performed with Terumo wires (curved and straight) as well as different catheters (Multipurpose/Vertebralis/Cobra). the unsuccessful recanalization attempt the laser catheter was applied. RESULTS: The application of laser angioplasty demonstrated a successful recanalization of the SFA in 76/94 patients (80.9%). In 18 patients (19.1%) the recanalization was not possible even with percutaneous transluminal laser angioplasty (PTLA). The reason for the unsuccessful PTLA was in 10 cases due to obstructing calcified material, which was resistant to PTLA application. In four cases obstructing calcifications caused the laser catheter to be positioned in subintimal tissue, resulting in perforation occlusion of the SFA. In another four patients there was an aberrant anatomy of the SFA which resulted in a direct vessel injury after advancing the laser catheter. After a follow-up period of 12 months primary, primary-assisted and secondary patency rates were 50.0%, 65.8% and 73.7%, respectively. DISCUSSION: In primarily unsuccessful recanalization of the SFA, PTLA allows in After 80% of cases a successful recanalization of the SFA. The technical success rate and the patency rate support the application of PTLA. (Int J Cardiovasc 2000; 3: 153–160) 相似文献