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101.
I Ogilvie S Jackson K Bartlett D M Turnbull 《Biochemical medicine and metabolic biology》1991,46(3):373-379
Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is a common inborn error of mitochondrial fatty acid oxidation. To determine if immunoreactive enzyme protein is present in patients with MCAD deficiency, we studied cultured skin fibroblasts from patients with the 985 point mutation, present in about 85% of cases, and cell lines from patients in which the point mutation is not present or only involves one allele. Immunoblotting studies, using a polyclonal antibody to the purified protein, showed an absence of immunoreactive protein in mitochondrial fractions prepared from fibroblasts from MCAD-deficient patients. To determine whether MCAD protein accumulated in the cytosol because of impaired transport into the mitochondria, we immunoprecipitated MCAD protein from the fibroblast homogenate. MCAD protein was detected in the immunoprecipitates from controls, but not in those from the MCAD-deficient patients. These results suggest that either the MCAD protein is not synthesised or, if produced, it is rapidly degraded. 相似文献
102.
Adolescent idiopathic scoliosis (AIS) is a clinically significant disorder with high heritability that affects 2–4% of the population. Genome-wide association studies have identified LBX1 as a strong susceptibility locus for AIS in Asian and Caucasian populations. Here we further dissect the genetic association with AIS in a Caucasian population. To identify genetic markers associated with AIS we employed a genome-wide association study (GWAS) design comparing 620 female Caucasian patients who developed idiopathic scoliosis during adolescence with 1,287 ethnically matched females who had normal spinal curves by skeletal maturity. The genomic region around LBX1 was imputed and haplotypes investigated for genetic signals under different inheritance models. The strongest signal was identified upstream of LBX1 (rs11190878, Ptrend = 4.18×10-9, OR = 0.63[0.54–0.74]). None of the remaining SNPs pass the genome-wide significance threshold. We found rs11190870, downstream of LBX1 and previously associated with AIS in Asian populations, to be in modest linkage disequilibrium (LD) with rs11190878 (r2 = 0.40, D'' = 0.81). Haplotype analysis shows that rs11190870 and rs11190878 track a single risk factor that resides on the ancestral haplotype and is shared across ethnic groups. We identify six haplotypes at the LBX1 locus including two strongly associated haplotypes; a recessive risk haplotype (TTA, Controlfreq = 0.52, P = 1.25×10-9, OR = 1.56), and a co-dominant protective haplotype (CCG, Controlfreq = 0.28, P = 2.75×10-7, OR = 0.65). Together the association signals from LBX1 explain 1.4% of phenotypic variance. Our results identify two clinically relevant haplotypes in the LBX1-region with opposite effects on AIS risk. The study demonstrates the utility of haplotypes over un-phased SNPs for individualized risk assessment by more strongly delineating individuals at risk for AIS without compromising the effect size. 相似文献
103.
Francois Lafortune Masad J. Damha Xuejun Tang Kenneth G. Standing John B. Westmore Kelvin K. Ogilvie 《Nucleosides, nucleotides & nucleic acids》2013,32(3):445-446
Abstract The negative ion mass spectra generated by a reflecting time-of-flight mass spectrometer are reported for a series of protected oligonucleotides. Quasimolecular and sequence ions have been detected, and the location and nature of protecting groups have been confirmed. 相似文献
104.
Kelvin K. Ogilvie H. R. Hanna Zbigniew Proba 《Nucleosides, nucleotides & nucleic acids》2013,32(2):169-183
Abstract A new series of acyclic nucleoside derivatives is described which contain two purine or pyrimidine rings (or a combination) attached to glycerol. The analogues described have been tested for activity against herpesviruses and were found to be inactive. 相似文献
105.
W. H. Ogilvie 《BMJ (Clinical research ed.)》1938,1(4039):1193-1198
106.
107.
Emma J. Adams Mary Goad Shannon Sahlqvist Fiona C. Bull Ashley R. Cooper David Ogilvie 《PloS one》2014,9(9)
Background
No current validated survey instrument allows a comprehensive assessment of both physical activity and travel behaviours for use in interdisciplinary research on walking and cycling. This study reports on the test-retest reliability and validity of physical activity measures in the transport and physical activity questionnaire (TPAQ).Methods
The TPAQ assesses time spent in different domains of physical activity and using different modes of transport for five journey purposes. Test-retest reliability of eight physical activity summary variables was assessed using intra-class correlation coefficients (ICC) and Kappa scores for continuous and categorical variables respectively. In a separate study, the validity of three survey-reported physical activity summary variables was assessed by computing Spearman correlation coefficients using accelerometer-derived reference measures. The Bland-Altman technique was used to determine the absolute validity of survey-reported time spent in moderate-to-vigorous physical activity (MVPA).Results
In the reliability study, ICC for time spent in different domains of physical activity ranged from fair to substantial for walking for transport (ICC = 0.59), cycling for transport (ICC = 0.61), walking for recreation (ICC = 0.48), cycling for recreation (ICC = 0.35), moderate leisure-time physical activity (ICC = 0.47), vigorous leisure-time physical activity (ICC = 0.63), and total physical activity (ICC = 0.56). The proportion of participants estimated to meet physical activity guidelines showed acceptable reliability (k = 0.60). In the validity study, comparison of survey-reported and accelerometer-derived time spent in physical activity showed strong agreement for vigorous physical activity (r = 0.72, p<0.001), fair but non-significant agreement for moderate physical activity (r = 0.24, p = 0.09) and fair agreement for MVPA (r = 0.27, p = 0.05). Bland-Altman analysis showed a mean overestimation of MVPA of 87.6 min/week (p = 0.02) (95% limits of agreement −447.1 to +622.3 min/week).Conclusion
The TPAQ provides a more comprehensive assessment of physical activity and travel behaviours and may be suitable for wider use. Its physical activity summary measures have comparable reliability and validity to those of similar existing questionnaires. 相似文献108.
Barlaam B Ballard P Bradbury RH Ducray R Germain H Hickinson DM Hudson K Kettle JG Klinowska T Magnien F Ogilvie DJ Olivier A Pearson SE Scott JS Suleman A Trigwell CB Vautier M Whittaker RD Wood R 《Bioorganic & medicinal chemistry letters》2008,18(2):674-678
Starting from initial lead 1 containing a basic 5-substituent, optimisation of the glycolamide-derived neutral 5-substituent led to potent inhibitors of erbB2 with good pharmacokinetics. Representative compounds 19 and 21 inhibited phosphorylation of erbB2 in a mouse BT474C xenograft model after oral administration. 相似文献
109.
1. Egg size is often used as a proxy of egg quality although size and composition may vary, e.g. in insects egg size usually decreases as female ages. Whether this decrease in size reflects reduced concentrations of essential nutrients such as lipids and proteins of eggs laid by ageing females, or does reduced size per se explain often observed lower fitness of later laid eggs is poorly explored. 2. Egg properties were compared with fitness parameters of offspring laid on the first and fourth night during the oviposition period of a capital breeding moth, Cleorodes lichenaria (Hufnagel). The study aim was to explore whether decreased egg size is caused by decreased provisioning into later laid eggs measured as egg protein and lipid concentration, and whether it results in lower fitness of later laid offspring. 3. The fresh and dry weight of eggs decreased over the oviposition period, but the protein and lipid concentration remained constant. Survival of larvae was lower among the fourth night laid offspring on a low quality host Parmelia sulcata Taylor compared to a high quality host Ramalina fraxinea (L.) Ach. No differences were observed in egg fertility or hatchability, neonate survival without food and pupal mass between the offspring produced on different nights. 4. Decreased survival of offspring produced later was rather attributable to absolute provisioning (i.e. lower weight of eggs) than relative provisioning (i.e. decreased concentrations of nutrients in eggs). It is argued that lower survival of later laid smaller eggs on low quality diet is likely attributable to physical and chemical characteristics of host lichens and/or physical properties of tiny neonate larvae. 相似文献
110.
Consistent linkage of dominantly inherited osteogenesis imperfecta to the type I collagen loci: COL1A1 and COL1A2 总被引:8,自引:4,他引:8 下载免费PDF全文
Bryan Sykes Donald Ogilvie Paul Wordsworth Gillian Wallis Chris Mathew Peter Beighton Alan Nicholls F. Michael Pope Elizabeth Thompson Petros Tsipouras Robin Schwartz Olafur Jensson Alfred Arnason Anne-Lise Brresen Arvid Heiberg Daniel Frey Beat Steinmann 《American journal of human genetics》1990,46(2):293-307
The segregation of COL1A1 and COL1A2, the two genes which encode the chains of type I collagen, was analyzed in 38 dominant osteogenesis imperfecta (OI) pedigrees by using polymorphic markers within or close to the genes. This was done in order to estimate the consistency of linkage of OI genes to these two loci. None of the 38 pedigrees showed evidence of recombination between the OI gene and both collagen loci, suggesting that the frequency of unlinked loci in the population must be low. From these results, approximate 95% confidence limits for the proportion of families linked to the type I collagen genes can be set between .91 and 1.00. This is high enough to base prenatal diagnosis of dominantly inherited OI on linkage to these genes even in families which are too small for the linkage to be independently confirmed to high levels of significance. When phenotypic features were compared with the concordant collagen locus, all eight pedigrees with Sillence OI type IV segregated with COL1A2. On the other hand, Sillence OI type I segregated with both COL1A1 (17 pedigrees) and COL1A2 (7 pedigrees). The concordant locus was uncertain in the remaining six OI type I pedigrees. Of several other features, the presence or absence of presenile hearing loss was the best predictor of the mutant locus in OI type I families, with 13 of the 17 COL1A1 segregants and none of the 7 COL1A2 segregants showing this feature. 相似文献