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71.
Melanocortin-1 receptor polymorphisms and risk of melanoma: is the association explained solely by pigmentation phenotype? 总被引:15,自引:0,他引:15
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Palmer JS Duffy DL Box NF Aitken JF O'Gorman LE Green AC Hayward NK Martin NG Sturm RA 《American journal of human genetics》2000,66(1):176-186
Risk of cutaneous malignant melanoma (CMM) is increased in sun-exposed whites, particularly those with a pale complexion. This study was designed to investigate the relationship of the melanocortin-1 receptor (MC1R) genotype to CMM risk, controlled for pigmentation phenotype. We report the occurrence of five common MC1R variants in an Australian population-based sample of 460 individuals with familial and sporadic CMM and 399 control individuals-and their relationship to such other risk factors as skin, hair, and eye color; freckling; and nevus count. There was a strong relationship between MC1R variants and hair color and skin type. Moreover, MC1R variants were found in 72% of the individuals with CMM, whereas only 56% of the control individuals carried at least one variant (P<.001), a finding independent of strength of family history of melanoma. Three active alleles (Arg151Cys, Arg160Trp, and Asp294His), previously associated with red hair, doubled CMM risk for each additional allele carried (odds ratio 2.0; 95% confidence interval 1. 6-2.6). No such independent association could be demonstrated with the Val60Leu and Asp84Glu variants. Among pale-skinned individuals alone, this association between CMM and MC1R variants was absent, but it persisted among those reporting a medium or olive/dark complexion. We conclude that the effect that MC1R variant alleles have on CMM is partly mediated via determination of pigmentation phenotype and that these alleles may also negate the protection normally afforded by darker skin coloring in some members of this white population. 相似文献
72.
We describe a method for measuring nociception in cattle using a CO(2) laser aimed at the caudal aspect of the metatarsi. In Experiment 1, infrared thermography showed that calves responded by lifting their legs when skin temperatures reached 45-55 degrees C. In Experiment 2a, the validity of the method was tested by comparing the response latencies of 14 calves to two power settings (2.25 W vs. 4.5 W) with each setting being applied six times. We found that both leg-lift latencies and tail-flick latencies were lower at the higher power setting, and the calves were more likely to respond by kicking than by simply moving the leg. The standard deviations between and within calves were smaller at the higher power setting, and the large within-calf variation means that at least three tests were required to obtain reliable measures that could differentiate between calves. In Experiment 2b, application of the laser at a range of power settings (2.0, 3.0, 4.0, 4.5, 5.0 and 5.5 W) on 16 calves showed that response latencies decreased as power increased up to 4.5 W, after which no further change occurred. In Experiment 3, the repeatability of the method was evaluated on nine measures with the high power setting (4.5 W). The coefficient of variation associated with repetition of the measures was 36%. In general, we found little change in response latencies with repeated use of the laser, except that responses on the second test tended to be shorter. Experiment 4 showed that ambient temperatures between 16 degrees C and 27 degrees C did not affect response latencies, but these were longer at temperatures of 7 degrees C. We suggest that the method is a useful way of measuring cattle's sensitivity to nociception as the animals need not be restrained and the distance to the animal need not be closely controlled. However, to obtain accurate, valid and reliable measures it is necessary to use a high power setting (4.5 W) and take at least three consecutive measures of the response latency. 相似文献
73.
Dating the origin of the CCR5-Delta32 AIDS-resistance allele by the coalescence of haplotypes. 总被引:14,自引:2,他引:12
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J C Stephens D E Reich D B Goldstein H D Shin M W Smith M Carrington C Winkler G A Huttley R Allikmets L Schriml B Gerrard M Malasky M D Ramos S Morlot M Tzetis C Oddoux F S di Giovine G Nasioulas D Chandler M Aseev M Hanson L Kalaydjieva D Glavac P Gasparini E Kanavakis M Claustres M Kambouris H Ostrer G Duff V Baranov H Sibul A Metspalu D Goldman N Martin D Duffy J Schmidtke X Estivill S J O'Brien M Dean 《American journal of human genetics》1998,62(6):1507-1515
The CCR5-Delta32 deletion obliterates the CCR5 chemokine and the human immunodeficiency virus (HIV)-1 coreceptor on lymphoid cells, leading to strong resistance against HIV-1 infection and AIDS. A genotype survey of 4,166 individuals revealed a cline of CCR5-Delta32 allele frequencies of 0%-14% across Eurasia, whereas the variant is absent among native African, American Indian, and East Asian ethnic groups. Haplotype analysis of 192 Caucasian chromosomes revealed strong linkage disequilibrium between CCR5 and two microsatellite loci. By use of coalescence theory to interpret modern haplotype genealogy, we estimate the origin of the CCR5-Delta32-containing ancestral haplotype to be approximately 700 years ago, with an estimated range of 275-1,875 years. The geographic cline of CCR5-Delta32 frequencies and its recent emergence are consistent with a historic strong selective event (e.g. , an epidemic of a pathogen that, like HIV-1, utilizes CCR5), driving its frequency upward in ancestral Caucasian populations. 相似文献
74.
Repeated Cocaine Administration Alters Extracellular Glutamate in the Ventral Tegmental Area 总被引:9,自引:5,他引:4
Abstract: The present study determined if repeated cocaine injections alter the effect of cocaine on extracellular glutamate in the ventral tegmental area (VTA). All rats were treated with daily cocaine (15 mg/kg i.p. × 2 days, 30 mg/kg i.p. × 5 days) or saline for 7 days. At 21 days after discontinuing the daily injections, a dialysis probe was placed into the VTA and the extracellular levels of glutamate were estimated. A systemic injection of cocaine (15 mg/kg i.p.) elevated extracellular glutamate in the VTA of rats pretreated with daily cocaine but not in the daily saline-pretreated subjects. No significant change in glutamate was produced by a saline injection in either pretreatment group. In a group of rats pretreated with daily cocaine, the D1 antagonist SCH-23390 (30 µ M ) was infused through the dialysis probe prior to the acute injections of saline and cocaine. SCH-23390 prevented the increase in extracellular glutamate associated with the acute administration of cocaine. Behavioral data were collected simultaneously with the measures of extracellular glutamate. The behavioral stimulant effect of cocaine was greater in cocaine-pretreated than saline-pretreated subjects, and the behavioral augmentation in cocaine-pretreated rats was partly blocked by SCH-23390. These data support the hypotheses that repeated cocaine administration produces an increase in the capacity of D1 receptor stimulation to release glutamate in the VTA and that this mechanism partly mediates behavioral sensitization produced in rats treated with daily cocaine injections. 相似文献
75.
Maguire TM Shering SG Duggan CM McDermott EW O'Higgins NJ Duffy MJ 《The International journal of biological markers》1998,13(3):139-144
Cathepsin B (CB) is a thiol-stimulated protease implicated in cancer invasion and metastasis. Other proteases involved in cancer spread such as urokinase-type plasminogen activator (uPA) and cathepsin D have previously been shown to be prognostic markers in breast cancer. CB was assayed by ELISA in 193 patients with primary breast cancer. CB levels were significantly higher in both primary and metastatic breast tumors than in fibroadenomas (p = 0.0001). In the primary carcinomas, CB levels showed no significant correlation with either nodal status, tumor size or estrogen receptor (ER) status. Patients with primary breast cancers containing high levels of CB had a significantly shorter disease-free interval (p = 0.01, chi-square = 6.61) and overall survival (p = 0.014, chi-square = 6.08) than patients with low levels of the protease. However, in multivariate analysis, using nodal status, tumor size, ER status and urokinase plasminogen activator (uPA), CB was not an independent prognostic marker. In contrast, nodal status, ER status and uPA were prognostic in multivariate analysis. In conclusion, CB, like certain other proteases implicated in cancer metastasis, correlates with poor outcome in patients with breast cancer. These results thus support the evidence from model systems linking CB to cancer spread. Inhibition of CB expression or activity might therefore be exploited for anti-metastatic therapies. 相似文献
76.
77.
Spectrometric studies on stability of tenuazonic acid (TeA) solution in organic solvents 总被引:1,自引:0,他引:1
The stability of tenuazonic acid solution at different temperatures and storage times was studied using methanol, methanol-water
(8:2 v/v), benzene and benzene-acetonitrile (98:2 v/v) as solvents. Solutions were analysed by a spectrometric method TeA
U.V.-spectrum was recorded. Results indicated that the optimum temperature for long-time storage period of tenuazonic acid
solution in any solvent assayed is -20°C. Benzene and benzene-acetonitrile (98:2 v/v) could be advised to make tenuazonic
acid solution which will be stored less than 2 months at 4°C. Methanol and methanolwater (8:2 v/v) are not recommended because
a low stability of TeA solution in this solvents. 相似文献
78.
Christine A. M. Smith Karine Toupin-April Jeffrey W. Jutai Ciarán M. Duffy Prinon Rahman Sabrina Cavallo Lucie Brosseau 《PloS one》2015,10(9)
Objectives
The objectives of this review are to: 1) appraise the methodological quality of clinical practice guidelines (CPGs) in juvenile idiopathic arthritis (JIA) providing pharmacological and/or non-pharmacological intervention recommendations, and 2) summarize the recommendations provided by the included CPGs and compare them where possible.Methods
A systematic search was performed. Three trained appraisers independently evaluated the methodological quality of the CPGs using a validated and reliable instrument, the Appraisal of Guidelines in Research and Evaluation II. Six domains were considered: 1) score and purpose; 2) stakeholder involvement; 3) rigor of development; 4) clarity of presentation; 5) applicability; and 6) editorial independence. The domains consist of a total of 23 items each scored on a 7-point scale. High quality CPGs were identified if they had a domain score above 60% in rigor of development, and two other domains.Results
Of the three included CPGs, the Royal Australian College of General Practitioners (RACGP) and American College of Rheumatology (ACR) CPGs were considered to be of high quality, but the German Society for Pediatric Rheumatology was of lower quality. Domains one to four had high domain scores across the guidelines (mean (standard deviation)): 72.76 (13.80); 66.67 (9.81); 64.67 (7.77); and 87.00 (9.64), respectively. Lower scores were obtained for applicability (14.00 (5.57)) and editorial independence (43.44 (7.02)). Recommendations varied across CPGs due to differences in context, target audience (general practitioners, rheumatologists, and other multidisciplinary healthcare professionals) and patients’ disease presentations. Despite this variability, progression of pharmacological treatment did not conflict between CPGs. Recommendations for non-pharmacological interventions were vague and the interventions considered varied between CPGs.Conclusions
Overall, recommendations were based on a paucity of evidence and weak study designs. Further research is needed on interventions in JIA, as well as higher quality CPGs to facilitate implementation of the best evidence-based recommendations in clinical practice. 相似文献79.
Frédégonde About Tiphaine Oudot-Mellakh Jonathan Niay Pascaline Rabiéga Vincent Pedergnana Darragh Duffy Philippe Sultanik Carole Cagnot Fabrice Carrat Patrick Marcellin Fabien Zoulim Dominique Larrey Christophe Hézode Hélène Fontaine Jean-Pierre Bronowicki Stanislas Pol Matthew L. Albert Ioannis Theodorou Aurélie Cobat Laurent Abel ANRS CO-CUPIC study group 《PloS one》2015,10(12)
Background
Human genetic factors influence the outcome of pegylated interferon and ribavirin hepatitis C therapy. We explored the role of IL28B, APOH and ITPA SNPs on the outcomes of triple therapy including telaprevir or boceprevir in patients with compensated cirrhosis chronically infected with HCV-1.Patients and Methods
A total of 256 HCV-1 Caucasian treatment-experienced patients with compensated cirrhosis from the ANRS CO20-CUPIC cohort were genotyped for a total of 10 candidate SNPs in IL28B (rs12979860 and rs368234815), APOH (rs8178822, rs12944940, rs10048158, rs52797880, rs1801689 and rs1801690) and ITPA (rs1127354 and rs7270101). We tested the association of IL28B and APOH SNPs with sustained virological response and of ITPA SNPs with anemia related phenotypes by means of logistic regression assuming an additive genetic model.Results
None of the six APOH SNPs were associated with sustained virological response. The favorable alleles of the IL28B SNPs rs12979860 and rs368234815 were associated with sustained virological response (rs12979860: OR = 2.35[1.50–3.70], P = 2x10-4). Refined analysis showed that the effect of IL28B SNPs on sustained virological response was restricted to prior PegIFN/RBV relapse (OR = 3.80[1.82–8.92], P = 8x10-4). We also confirmed the association between ITPA low activity alleles and protection against early hemoglobin decline in triple therapy (P = 2x10-5).Conclusion
Our results suggest that the screening of rs12979860 may remain interesting for decision making in prior relapse HCV-1 Caucasian patients with compensated cirrhosis eligible for a telaprevir- or boceprevir-based therapy. 相似文献80.
Carolina I. Cura Tomas Duffy Raúl H. Lucero Margarita Bisio Julie Péneau Matilde Jimenez-Coello Eva Calabuig María J. Gimenez Edward Valencia Ayala Sonia A. Kjos José Santalla Susan M. Mahaney Nelly M. Cayo Claudia Nagel Laura Barcán Edith S. Málaga Machaca Karla Y. Acosta Viana Laurent Brutus Susana B. Ocampo Christine Aznar Cesar A. Cuba Cuba Ricardo E. Gürtler Janine M. Ramsey Isabela Ribeiro John L. VandeBerg Zaida E. Yadon Antonio Osuna Alejandro G. Schijman 《PLoS neglected tropical diseases》2015,9(5)