全文获取类型
收费全文 | 377篇 |
免费 | 36篇 |
出版年
2022年 | 1篇 |
2021年 | 12篇 |
2020年 | 4篇 |
2019年 | 8篇 |
2018年 | 9篇 |
2017年 | 12篇 |
2016年 | 10篇 |
2015年 | 19篇 |
2014年 | 30篇 |
2013年 | 26篇 |
2012年 | 25篇 |
2011年 | 31篇 |
2010年 | 20篇 |
2009年 | 20篇 |
2008年 | 18篇 |
2007年 | 16篇 |
2006年 | 17篇 |
2005年 | 16篇 |
2004年 | 30篇 |
2003年 | 24篇 |
2002年 | 17篇 |
2001年 | 4篇 |
2000年 | 2篇 |
1998年 | 5篇 |
1997年 | 5篇 |
1996年 | 2篇 |
1995年 | 3篇 |
1994年 | 2篇 |
1993年 | 1篇 |
1992年 | 2篇 |
1991年 | 2篇 |
1990年 | 3篇 |
1989年 | 1篇 |
1986年 | 1篇 |
1985年 | 2篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1981年 | 2篇 |
1975年 | 1篇 |
1974年 | 1篇 |
1971年 | 1篇 |
1970年 | 1篇 |
1968年 | 1篇 |
1960年 | 1篇 |
1959年 | 1篇 |
1958年 | 1篇 |
1927年 | 1篇 |
排序方式: 共有413条查询结果,搜索用时 250 毫秒
211.
212.
213.
Plant functional types do not predict biomass responses to removal and fertilization in Alaskan tussock tundra 总被引:1,自引:0,他引:1
214.
215.
Agnes Rasmuson Lova Segerstr?m Maria Nethander Jennie Finnman Lotta H. M. Elfman Niloufar Javanmardi Staffan Nilsson John Inge Johnsen Tommy Martinsson Per Kogner 《PloS one》2012,7(12)
Background
The TH-MYCN transgenic neuroblastoma model, with targeted MYCN expression to the developing neural crest, has been used to study neuroblastoma development and evaluate novel targeted tumor therapies.Methods
We followed tumor development in 395 TH-MYCN (129X1/SvJ) mice (125 negative, 206 hemizygous and 64 homozygous mice) by abdominal palpations up to 40 weeks of age. DNA sequencing of MYCN in the original plasmid construct and mouse genomic DNA was done to verify the accuracy. Copy number analysis with Affymetrix® Mouse Diversity Genotyping Arrays was used to characterize acquired genetic aberrations.Results
DNA sequencing confirmed presence of human MYCN cDNA in genomic TH-MYCN DNA corresponding to the original plasmid construct. Tumor incidence and growth correlated significantly to transgene status with event-free survival for hemizygous mice at 50%, and 0% for homozygous mice. Hemizygous mice developed tumors at 5.6–19 weeks (median 9.1) and homozygous mice at 4.0–6.9 weeks (5.4). The mean treatment window, time from palpable tumor to sacrifice, for hemizygous and homozygous mice was 15 and 5.2 days, respectively. Hemizygous mice developing tumors as early as homozygous mice had a longer treatment window. Age at tumor development did not influence treatment window for hemizygous mice, whereas treatment window in homozygous mice decreased significantly with increasing age. Seven out of 10 analysed tumors had a flat DNA profile with neither segmental nor numerical chromosomal aberrations. Only three tumors from hemizygous mice showed acquired genetic features with one or more numerical aberrations. Of these, one event corresponded to gain on the mouse equivalent of human chromosome 17.Conclusion
Hemizygous and homozygous TH-MYCN mice have significantly different neuroblastoma incidence, tumor growth characteristics and treatment windows but overlap in age at tumor development making correct early genotyping essential to evaluate therapeutic interventions. Contrasting previous studies, our data show that TH-MYCN tumors have few genetic aberrations. 相似文献216.
217.
Castellana NE McCutcheon K Pham VC Harden K Nguyen A Young J Adams C Schroeder K Arnott D Bafna V Grogan JL Lill JR 《Proteomics》2011,11(3):395-405
A mouse hybridoma antibody directed against a member of the tumour necrosis factor (TNF)-superfamily, lymphotoxin-alpha (LT-α), was isolated from stored mouse ascites and purified to homogeneity. After more than a decade of storage the genetic material was not available for cloning; however, biochemical assays with the ascites showed this antibody against LT-α (LT-3F12) to be a preclinical candidate for the treatment of several inflammatory pathologies. We have successfully rescued the LT-3F12 antibody by performing MS analysis, primary amino acid sequence determination by template proteogenomics, and synthesis of the corresponding recombinant DNA by reverse engineering. The resurrected antibody was expressed, purified and shown to demonstrate the desired specificity and binding properties in a panel of immuno-biochemical tests. The work described herein demonstrates the powerful combination of high-throughput informatic proteomic de novo sequencing with reverse engineering to reestablish monoclonal antibody-expressing cells from archived protein sample, exemplifying the development of novel therapeutics from cryptic protein sources. 相似文献
218.
Chen J Brunzell DH Jackson K van der Vaart A Ma JZ Payne TJ Sherva R Farrer LA Gejman P Levinson DF Holmans P Aggen SH Damaj I Kuo PH Webb BT Anton R Kranzler HR Gelernter J Li MD Kendler KS Chen X 《PloS one》2011,6(12):e28790
Individuals with schizophrenia tend to be heavy smokers and are at high risk for tobacco dependence. However, the nature of the comorbidity is not entirely clear. We previously reported evidence for association of schizophrenia with SNPs and SNP haplotypes in a region of chromosome 5q containing the SPEC2, PDZ-GEF2 and ACSL6 genes. In this current study, analysis of the control subjects of the Molecular Genetics of Schizophrenia (MGS) sample showed similar pattern of association with number of cigarettes smoked per day (numCIG) for the same region. To further test if this locus is associated with tobacco smoking as measured by numCIG and FTND, we conducted replication and meta-analysis in 12 independent samples (n>16,000) for two markers in ACSL6 reported in our previous schizophrenia study. In the meta-analysis of the replication samples, we found that rs667437 and rs477084 were significantly associated with numCIG (p = 0.00038 and 0.00136 respectively) but not with FTND scores. We then used in vitro and in vivo techniques to test if nicotine exposure influences the expression of ACSL6 in brain. Primary cortical culture studies showed that chronic (5-day) exposure to nicotine stimulated ACSL6 mRNA expression. Fourteen days of nicotine administration via osmotic mini pump also increased ACSL6 protein levels in the prefrontal cortex and hippocampus of mice. These increases were suppressed by injection of the nicotinic receptor antagonist mecamylamine, suggesting that elevated expression of ACSL6 requires nicotinic receptor activation. These findings suggest that variations in the ACSL6 gene may contribute to the quantity of cigarettes smoked. The independent associations of this locus with schizophrenia and with numCIG in non-schizophrenic subjects suggest that this locus may be a common liability to both conditions. 相似文献
219.
Gosby AK Conigrave AD Lau NS Iglesias MA Hall RM Jebb SA Brand-Miller J Caterson ID Raubenheimer D Simpson SJ 《PloS one》2011,6(10):e25929
A significant contributor to the rising rates of human obesity is an increase in energy intake. The ‘protein leverage hypothesis’ proposes that a dominant appetite for protein in conjunction with a decline in the ratio of protein to fat and carbohydrate in the diet drives excess energy intake and could therefore promote the development of obesity. Our aim was to test the ‘protein leverage hypothesis’ in lean humans by disguising the macronutrient composition of foods offered to subjects under ad libitum feeding conditions. Energy intakes and hunger ratings were measured for 22 lean subjects studied over three 4-day periods of in-house dietary manipulation. Subjects were restricted to fixed menus in random order comprising 28 foods designed to be similar in palatability, availability, variety and sensory quality and providing 10%, 15% or 25% energy as protein. Nutrient and energy intake was calculated as the product of the amount of each food eaten and its composition. Lowering the percent protein of the diet from 15% to 10% resulted in higher (+12±4.5%, p = 0.02) total energy intake, predominantly from savoury-flavoured foods available between meals. This increased energy intake was not sufficient to maintain protein intake constant, indicating that protein leverage is incomplete. Urinary urea on the 10% and 15% protein diets did not differ statistically, nor did they differ from habitual values prior to the study. In contrast, increasing protein from 15% to 25% did not alter energy intake. On the fourth day of the trial, however, there was a greater increase in the hunger score between 1–2 h after the 10% protein breakfast versus the 25% protein breakfast (1.6±0.4 vs 25%: 0.5±0.3, p = 0.005). In our study population a change in the nutritional environment that dilutes dietary protein with carbohydrate and fat promotes overconsumption, enhancing the risk for potential weight gain. 相似文献
220.
Jennie B?ck Christian Lood Anders A Bengtsson Kristina Nilsson Ekdahl Bo Nilsson 《Arthritis research & therapy》2013,15(6):R206