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681.
Direct and social genetic parameters for growth and fin damage traits in Atlantic cod (Gadus morhua)
Hanne M Nielsen Brage B Monsen J?rgen ?deg?rd Piter Bijma B?rge Damsg?rd Hilde Toften Ingrid Olesen 《遗传、选种与进化》2014,46(1):5
Background
The aim of the study was to estimate genetic parameters for direct and social genetic effects (SGE) for growth and welfare traits in farmed Atlantic cod (Gadus morhua). A SGE refers to the effect of an individual’s genes on trait performance of its social partners. In total, 2100 individually tagged juveniles from 100 families at an average age of 222 days post-hatching were used. Each family was separated into three groups of seven fish, and were randomly assigned to 100 experimental tanks, together with fish from two other families. Body weight and length of the first, second and third dorsal fin and the caudal fin measured by digital image analysis were measured at the start of the experiment, after two weeks, and after six weeks. Fin erosion was scored subjectively after six weeks. Variance components estimated using a conventional animal model were compared to those of an animal model including a SGE.Results
Heritabilities from the conventional animal model ranged from 0.24 to 0.34 for body weight and 0.05 to 0.80 for fin length. Heritabilities for fin erosion were highest for the first dorsal fin (0.83 ± 0.08, mean ± standard error) and lowest for the third dorsal fin (0.01 ± 0.04). No significant SGE were found for body weight, whereas SGE for fin lengths were significant after two and six weeks. Contributions to the total heritable variance were equal to 21.5% (6.1 ± 2.1) for the direct effect, 33.1% (9.4 ± 3.2) for the direct-social covariance, and 45.4% (12.9 ± 4.1) for the social variance for length of the first dorsal fin. For fin erosion, SGE were only significant for the second and third dorsal fin.Conclusions
Including SGE for fin length and fin erosion in the animal model increased the estimated heritable variation. However, estimates of total heritable variances were inaccurate and a larger experiment is needed to accurately quantify total heritable variance. Despite this, our results demonstrate that considering social breeding values for fin length or fin erosion when selecting fish will enable us to improve response to selection for welfare traits in Atlantic cod juveniles. 相似文献682.
Eveline A. Martens Blandine Gatta-Cherifi Hanne K. Gonnissen Margriet S. Westerterp-Plantenga 《PloS one》2014,9(10)
Background
Protein supplementation has been shown to reduce the increases in intrahepatic triglyceride (IHTG) content induced by acute hypercaloric high-fat and high-fructose diets in humans.Objective
To assess the effect of a 12-wk iso-energetic high protein-low carbohydrate (HPLC) diet compared with an iso-energetic high carbohydrate-low protein (HCLP) diet on IHTG content in healthy non-obese subjects, at a constant body weight.Design
Seven men and nine women [mean ± SD age: 24±5 y; BMI: 22.9±2.1 kg/m2] were randomly allocated to a HPLC [30/35/35% of energy (En%) from protein/carbohydrate/fat] or a HCLP (5/60/35 En%) diet by stratification on sex, age and BMI. Dietary guidelines were prescribed based on individual daily energy requirements. IHTG content was measured by 1H-magnetic resonance spectroscopy before and after the dietary intervention.Results
IHTG content changed in different directions with the HPLC (CH2H2O: 0.23±0.17 to 0.20±0.10; IHTG%: 0.25±0.20% to 0.22±0.11%) compared with the HCLP diet (CH2H2O: 0.34±0.20 vs. 0.38±0.21; IHTG%: 0.38±0.22% vs. 0.43±0.24%), which resulted in a lower IHTG content in the HPLC compared with the HCLP diet group after 12 weeks, which almost reached statistical significance (P = 0.055).Conclusions
A HPLC vs. a HCLP diet has the potential to preserve vs. enlarge IHTG content in healthy non-obese subjects at a constant body weight.Trial Registration
Clinicaltrials.gov NCT01551238相似文献683.
684.
Hanne A. Askautrud Elisabet Gjernes Gjermund Gunnes Marit Sletten Douglas T. Ross Anne Lise B?rresen-Dale Nina Iversen Michael A. Tranulis Eirik Frengen 《PloS one》2014,9(1)
N-myc downstream-regulated gene 1 (NDRG1) is induced by cellular stress such as hypoxia and DNA damage, and in humans, germ line mutations cause Charcot-Marie-Tooth disease. However, the cellular roles of NDRG1 are not fully understood. Previously, NDRG1 was shown to mediate doxorubicin resistance under hypoxia, suggesting a role for NDRG1 in cell survival under these conditions. We found decreased apoptosis in doxorubicin-treated cells expressing NDRG1 shRNAs under normoxia, demonstrating a requirement for NDRG1 in apoptosis in breast epithelial cells under normal oxygen pressure. Also, different cellular stress regimens, such as hypoxia and doxorubicin treatment, induced NDRG1 through different stress signalling pathways. We further compared expression profiles in human breast epithelial cells ectopically over-expressing NDRG1 with cells expressing NDRG1 shRNAs in order to identify biological pathways where NDRG1 is involved. The results suggest that NDRG1 may have roles connected to vesicle transport. 相似文献
685.
Background
In colorectal cancer a distinct subgroup of tumours demonstrate the CpG island methylator phenotype (CIMP). However, a consensus of how to score CIMP is not reached, and variation in definition may influence the reported CIMP prevalence in tumours. Thus, we sought to compare currently suggested definitions and cut-offs for methylation markers and how they influence CIMP classification in colon cancer.Methods
Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA), with subsequent fragment analysis, was used to investigate methylation of tumour samples. In total, 31 CpG sites, located in 8 different genes (RUNX3, MLH1, NEUROG1, CDKN2A, IGF2, CRABP1, SOCS1 and CACNA1G) were investigated in 64 distinct colon cancers and 2 colon cancer cell lines. The Ogino gene panel includes all 8 genes, in addition to the Weisenberger panel of which only 5 of the 8 genes included were investigated. In total, 18 alternative combinations of scoring of CIMP positivity on probe-, gene-, and panel-level were analysed and compared.Results
For 47 samples (71%), the CIMP status was constant and independent of criteria used for scoring; 34 samples were constantly scored as CIMP negative, and 13 (20%) consistently scored as CIMP positive. Only four of 31 probes (13%) investigated showed no difference in the numbers of positive samples using the different cut-offs. Within the panels a trend was observed that increasing the gene-level stringency resulted in a larger difference in CIMP positive samples than increasing the probe-level stringency. A significant difference between positive samples using ‘the most stringent’ as compared to ‘the least stringent’ criteria (20% vs 46%, respectively; p<0.005) was demonstrated.Conclusions
A statistical significant variation in the frequency of CIMP depending on the cut-offs and genes included in a panel was found, with twice as many positives samples by least compared to most stringent definition used. 相似文献686.
Geoffrey R. Bennett Ryan Peters Xiao-hong Wang Jeungphill Hanne Robert W. Sobol Ralf Bundschuh Richard Fishel Kristine E. Yoder 《PloS one》2014,9(7)
Host base excision repair (BER) proteins that repair oxidative damage enhance HIV infection. These proteins include the oxidative DNA damage glycosylases 8-oxo-guanine DNA glycosylase (OGG1) and mutY homolog (MYH) as well as DNA polymerase beta (Polβ). While deletion of oxidative BER genes leads to decreased HIV infection and integration efficiency, the mechanism remains unknown. One hypothesis is that BER proteins repair the DNA gapped integration intermediate. An alternative hypothesis considers that the most common oxidative DNA base damages occur on guanines. The subtle consensus sequence preference at HIV integration sites includes multiple G:C base pairs surrounding the points of joining. These observations suggest a role for oxidative BER during integration targeting at the nucleotide level. We examined the hypothesis that BER repairs a gapped integration intermediate by measuring HIV infection efficiency in Polβ null cell lines complemented with active site point mutants of Polβ. A DNA synthesis defective mutant, but not a 5′dRP lyase mutant, rescued HIV infection efficiency to wild type levels; this suggeted Polβ DNA synthesis activity is not necessary while 5′dRP lyase activity is required for efficient HIV infection. An alternate hypothesis that BER events in the host genome influence HIV integration site selection was examined by sequencing integration sites in OGG1 and MYH null cells. In the absence of these 8-oxo-guanine specific glycosylases the chromatin elements of HIV integration site selection remain the same as in wild type cells. However, the HIV integration site sequence preference at G:C base pairs is altered at several positions in OGG1 and MYH null cells. Inefficient HIV infection in the absence of oxidative BER proteins does not appear related to repair of the gapped integration intermediate; instead oxidative damage repair may participate in HIV integration site preference at the sequence level. 相似文献
687.
Staphylococcus aureus Transcriptome Architecture: From Laboratory to Infection-Mimicking Conditions 总被引:1,自引:0,他引:1
Ulrike M?der Pierre Nicolas Maren Depke Jan Pané-Farré Michel Debarbouille Magdalena M. van der Kooi-Pol Cyprien Guérin Sandra Dérozier Aurelia Hiron Hanne Jarmer Aurélie Leduc Stephan Michalik Ewoud Reilman Marc Schaffer Frank Schmidt Philippe Bessières Philippe Noirot Michael Hecker Tarek Msadek Uwe V?lker Jan Maarten van Dijl 《PLoS genetics》2016,12(4)
688.
Camilla Stampe Jensen Shoji Watanabe Hanne Borger Rasmussen Nicole Schmitt S?ren-Peter Olesen Nicholas A. Frost Thomas A. Blanpied Hiroaki Misonou 《The Journal of biological chemistry》2014,289(15):10566-10581
Proper membrane localization of ion channels is essential for the function of neuronal cells. Particularly, the computational ability of dendrites depends on the localization of different ion channels in specific subcompartments. However, the molecular mechanisms that control ion channel localization in distinct dendritic subcompartments are largely unknown. Here, we developed a quantitative live cell imaging method to analyze protein sorting and post-Golgi vesicular trafficking. We focused on two dendritic voltage-gated potassium channels that exhibit distinct localizations: Kv2.1 in proximal dendrites and Kv4.2 in distal dendrites. Our results show that Kv2.1 and Kv4.2 channels are sorted into two distinct populations of vesicles at the Golgi apparatus. The targeting of Kv2.1 and Kv4.2 vesicles occurred by distinct mechanisms as evidenced by their requirement for specific peptide motifs, cytoskeletal elements, and motor proteins. By live cell and super-resolution imaging, we identified a novel trafficking machinery important for the localization of Kv2.1 channels. Particularly, we identified non-muscle myosin II as an important factor in Kv2.1 trafficking. These findings reveal that the sorting of ion channels at the Golgi apparatus and their subsequent trafficking by unique molecular mechanisms are crucial for their specific localizations within dendrites. 相似文献
689.
Oxidation of bovine serum albumin (BSA) was investigated using different oxidants: The water-soluble azo-initiator 2,2'azo-bis-(2-amidinopropane) hydrochloride (AAPH), a combination of FeCl3 and ascorbate or the Fenton oxidant consisting of FeCl2, H2O2 and EDTA. In addition, the effects of exogenous compounds such as tert-butyl hydroperoxide (tBuOOH) or solvents such as tetrahydrofuran (THF), often used in model systems, was evaluated. The extent of protein damage was studied by measuring protein carbonyl groups and protein hydroperoxides. The interaction between Fenton oxidant and EDTA, THF or tBuOOH was further characterized using spin trapping electron spin resonance (ESR) spectroscopy. The results showed that the extent of protein oxidation depended on the oxidant used. The Fenton oxidant was the most reactive of the initiators tested. However, in the absence of EDTA, the Fenton system produced protein carbonyl groups on BSA equivalent to that obtained with the other oxidants, however, significantly more protein hydroperoxide was produced. Surprisingly, it was also found that addition of tBuOOH or THF to BSA reduced protein damage when the oxidation was initiated with the Fenton oxidant. ESR investigation showed that EDTA played a key role in the generation of free radicals. It was also revealed that in an EDTA containing system both tBuOOH and THF were able to react with radicals without inducing protein damage in effect protecting BSA from oxidative damage. 相似文献
690.
Pecchi S Renhowe PA Taylor C Kaufman S Merritt H Wiesmann M Shoemaker KR Knapp MS Ornelas E Hendrickson TF Fantl W Voliva CF 《Bioorganic & medicinal chemistry letters》2010,20(23):6895-6898
PI3 Kinases are a family of lipid kinases mediating numerous cell processes such as proliferation, migration, and differentiation. The PI3 kinase pathway is often de-regulated in cancer through PI3Kα overexpression, gene amplification, mutations, and PTEN phosphatase deletion. PI3K inhibitors represent therefore an attractive therapeutic modality for cancer treatment. Herein we describe a novel series of PI3K inhibitors sharing a pyrimidine core and showing significant potency against class I PI3 kinases in the biochemical assay and in cells. The discovery, synthesis and SAR of this chemotype are described. 相似文献