全文获取类型
收费全文 | 368篇 |
免费 | 27篇 |
出版年
2023年 | 3篇 |
2022年 | 9篇 |
2021年 | 14篇 |
2020年 | 5篇 |
2019年 | 9篇 |
2018年 | 13篇 |
2017年 | 12篇 |
2016年 | 18篇 |
2015年 | 20篇 |
2014年 | 27篇 |
2013年 | 24篇 |
2012年 | 41篇 |
2011年 | 23篇 |
2010年 | 16篇 |
2009年 | 13篇 |
2008年 | 28篇 |
2007年 | 21篇 |
2006年 | 31篇 |
2005年 | 13篇 |
2004年 | 4篇 |
2003年 | 14篇 |
2002年 | 16篇 |
2001年 | 4篇 |
2000年 | 2篇 |
1999年 | 3篇 |
1997年 | 1篇 |
1996年 | 1篇 |
1994年 | 1篇 |
1993年 | 1篇 |
1990年 | 2篇 |
1987年 | 1篇 |
1985年 | 1篇 |
1981年 | 1篇 |
1979年 | 1篇 |
1973年 | 1篇 |
1971年 | 1篇 |
排序方式: 共有395条查询结果,搜索用时 2 毫秒
81.
82.
Geographic patterns of genetic differentiation have long been used to understand population history and to learn about the biological mechanisms of adaptation. Here we present an examination of genomic patterns of differentiation between northern and southern populations of Australian and North American Drosophila simulans, with an emphasis on characterizing signals of parallel differentiation. We report on the genomic scale of differentiation and functional enrichment of outlier SNPs. While, overall, signals of shared differentiation are modest, we find the strongest support for parallel differentiation in genomic regions that are associated with regulation. Comparisons to Drosophila melanogaster yield potential candidate genes involved in local adaptation in both species, providing insight into common selective pressures and responses. In contrast to D. melanogaster, in D. simulans we observe patterns of variation that are inconsistent with a model of temperate adaptation out of a tropical ancestral range, highlighting potential differences in demographic and colonization histories of this cosmopolitan species pair. 相似文献
83.
Xiaohong R. Yang Melissa Rotunno Yanzi Xiao Christian Ingvar Hildur Helgadottir Lorenza Pastorino Remco van Doorn Hunter Bennett Cole Graham Joshua N. Sampson Michael Malasky Aurelie Vogt Bin Zhu Giovanna Bianchi-Scarra William Bruno Paola Queirolo Giuseppe Fornarini Johan Hansson Rainer Tuominen Laurie Burdett Belynda Hicks Amy Hutchinson Kristine Jones Meredith Yeager Stephen J. Chanock Maria Teresa Landi Veronica Höiom Håkan Olsson Nelleke Gruis Paola Ghiorzo Margaret A. Tucker Alisa M. Goldstein 《Human genetics》2016,135(11):1241-1249
84.
85.
Alisa W. Coffin Timothy C. Strickland William F. Anderson Marshall C. Lamb Richard R. Lowrance Coby M. Smith 《Bioenergy Research》2016,9(2):587-600
With global increases in the production of cellulosic biomass for fuel, or “biofuel,” concerns over potential negative effects of using land for biofuel production have promoted attention to concepts of agricultural landscape design that sustainably balance tradeoffs between food, fuel, fiber, and conservation. The Energy Independence Security Act (EISA) of 2007 mandates an increase in advanced biofuels to 21 billion gallons in 2022. The southeastern region of the USA has been identified as a contributor to meeting half of this goal. We used a GIS-based approach to estimate the production and N-removal potential of three perennial biofeedstocks planted as conservation buffers (field borders associated with riparian buffers, and grassed waterways) on the Coastal Plain of Georgia, USA. Land cover, hydrology, elevation, and soils data were used to identify locations within agricultural landscapes that are most susceptible to runoff, erosion, and nutrient loss. We estimated potential annual biomass production from these areas to be: 2.5–3.5 Tg for giant miscanthus (Miscanthus?×?giganteus), 2–8.6 Tg for “Merkeron” napier grass (Pennisetum purpureum), and 1.9–7.5 Tg for “Alamo” switchgrass (Panicum virgatum). When production strategies were taken into consideration, we estimated total biomass yield of perennial grasses for the Georgia Coastal Plain at 2.2–9.4 Tg year?1. Using published rates of N removal and ethanol conversion, we calculated the amount of potential N removal by these systems as 8100–51,000 Mg year?1 and ethanol fuel production as 778–3296 Ml year?1 (206 to 871 million gal. US). 相似文献
86.
Claudio Fortis Elisabetta Ferrero Carlo Besana Mauro Biffi Silvia Heltai Laura Galli Anna Borri Alisa Schoenheit Claudio Rugarli 《Cancer immunology, immunotherapy : CII》1990,32(3):161-166
Summary The efficacy of recombinant interleukin-2 (rIL-2) or rIL-2 plus lymphokine-activated killer (LAK) cells in cancer therapy has been demonstrated by several groups both in experimental models in animals and clinical trials in humans, but their effects in vivo have yet to be clarified.Starting February 1988, we have treated 12 patients affected by advanced renal cancer with rIL-2 + LAK cells according to an open, non-randomized, phase II trial. Immediately before each rIL-2 infusion and during the last day of infusion, immunological tests were performed on the patients' peripheral blood mononuclear cells. During rIL-2 infusion we have observed a slight increase of the spontaneous cell proliferation and of natural killer (NK) and LAK activity; phenotypic analysis showed a significant decrease in the CD4+ T-lymphocyte subset, both in percentage and in absolute number. Conversely, before each cycle CD4+ cells increased when compared to basal values. No significant variations were observed in the CD8+ T-lymphocyte subset. Furthermore, a significant increase of the NK cells (CD3– CD56+ CD16+) was evident during rIL-2 infusion. 相似文献
87.
Zeynep M. Coskun Alisa B. Beydogan Sema Bolkent 《Journal of biochemical and molecular toxicology》2019,33(10)
The aim of the study is to clarify the effect of ghrelin treatment on the messenger RNA (mRNA) expression of the cannabinoid receptor 1 (Cnr1/CB1) and glucagon‐like peptide 1 receptor (Glp1r/GLP‐1R) as well as microRNAs (miR)‐122 and miR‐33a in the liver of rats with type 2 diabetes mellitus (T2DM). Adult Sprague‐Dawley rats were divided into three groups: control (n = 7), T2DM (n = 7), and treatment (n = 7). Control animals received tap water. T2DM was induced by feeding 10% fructose in drinking water for 2 weeks followed by a single injection of streptozotocin (40 mg/kg, intraperitoneally [IP]). In the treatment group, diabetic rats were injected ghrelin (25 μg/kg, IP) for 14 days. Serum lipid profiles were evaluated, and mRNA expression levels of Cnr1 and Glp1r in the liver were detected using quantitative real‐time polymerase chain reaction (RT‐qPCR). In addition, miR‐122 and miR‐33a levels were measured using RT‐qPCR. Serum triglycerides, low‐density lipoprotein cholesterol, and very‐low‐density lipoprotein cholesterol significantly increased in the T2DM group compared with control rats but ghrelin treatment showed no effect on serum lipid levels. The mRNA expression levels of Cnr1 and Glp1r decreased in the T2DM group compared with the control group. These reductions were significantly increased in the T2DM group treated with ghrelin. Furthermore, the increase in miR‐33a expression level was reduced in the treatment group compared to rats with T2DM. Our findings suggested that ghrelin treatment may alter the mRNA expression levels of CB1 and GLP‐1R in the liver of rats with T2DM. The mRNA levels of Cnr1 and Glp1r may inversely correlate with the expression level of miR‐33a but not miR‐122. 相似文献
88.
The focal adhesion kinase (FAK) family kinases, including FAK and proline-rich kinase 2 (Pyk)2, are the predominant mediators
of integrin αvβ3 signaling events that play an important role in cell adhesion, osteoclast pathology, and angiogenesis, all
processes important in rheumatoid arthritis (RA). Using immunohistochemical and western blot analysis, we studied the distribution
of phospho (p)FAK, pPyk2, pSrc, pPaxillin and pPLCγ in the synovial tissue (ST) from patients with RA, osteoarthritis (OA)
and normal donors (NDs) as well as in RA ST fibroblasts and peripheral blood differentiated macrophages (PB MΦs) treated with
tumor necrosis factor-α (TNFα) or interleukin-1β (IL1β). RA and OA STs showed a greater percentage of pFAK on lining cells
and MΦs compared with ND ST. RA ST fibroblasts expressed pFAK at baseline, which increased with TNFα or IL1β stimulation.
Pyk2 and Src were phosphorylated more on RA versus OA and ND lining cells and MΦs. pPyk2 was expressed on RA ST fibrobasts
but not in MΦs at baseline, however it was upregulated upon TNFα or IL1β activation in both cell types. pSrc was expressed
in RA ST fibroblasts and MΦs at baseline and was further increased by TNFα or IL1β stimulation. pPaxillin and pPLCγ were upregulated
in RA versus OA and ND lining cells and sublining MΦs. Activation of the FAK family signaling cascade on RA and OA lining
cells may be responsible for cell adhesion and migration into the diseased STs. Therapies targeting this novel signaling pathway
may be beneficial in RA. 相似文献
89.
New insights into innate immunity in Arabidopsis 总被引:2,自引:0,他引:2
The term innate immunity has been described as '. . . the surveillance system that detects the presence and nature of the infection and provides the first line of host defense . . .' (Medzhitov, 2001; Nat Rev Immunol 1: 135-145). The strategy of innate immunity is based on the recognition of constitutive and conserved molecules from pathogens by specific receptors, triggering defence responses (Medzhitov and Janeway, 2002; Science 296: 298-300). It has been only within the past few years that studies of plant innate immunity, especially in Arabidopsis, have provided important insights into molecular details that define innate immunity in plants. Here we review the innate immune response in Arabidopsis, where leucine-rich repeat (LRR) cell surface receptors play central roles in monitoring the presence of pathogen (microbe) associated molecules to initiate the rapid expression of defence genes. The PAMPS also activate the expression of genes encoding a family of endogenous peptides (AtPep1 paralogues) and their receptor (PEPR1) that amplify defence signalling through a feedback loop initiated by PAMPS. The concept of innate immunity has provided a valuable framework for researchers to re-evaluate the roles of exogenous and endogenous signals that regulate the expression of plant defensive genes. 相似文献
90.
Identification of potential tumor differentiation factor (TDF) receptor from steroid-responsive and steroid-resistant breast cancer cells 总被引:2,自引:0,他引:2
Sokolowska I Woods AG Gawinowicz MA Roy U Darie CC 《The Journal of biological chemistry》2012,287(3):1719-1733
Tumor differentiation factor (TDF) is a recently discovered protein, produced by the pituitary gland and secreted into the bloodstream. TDF and TDF-P1, a 20-amino acid peptide selected from the open reading frame of TDF, induce differentiation in human breast and prostate cancer cells but not in other cells. TDF protein has no identified site of action or receptor, and its mechanism of action is unknown. Here, we used TDF-P1 to purify and identify potential TDF receptor (TDF-R) candidates from MCF7 steroid-responsive breast cancer cells and non-breast HeLa cancerous cells using affinity purification chromatography (AP), and mass spectrometry (MS). We identified four candidate proteins from the 70-kDa heat shock protein (HSP70) family in MCF7 cells. Experiments in non-breast HeLa cancerous cells did not identify any TDF-R candidates. AP and MS experiments were validated by AP and Western blotting (WB). We additionally looked for TDF-R in steroid-resistant BT-549 cells and human dermal fibroblasts (HDF-a) using AP and WB. TDF-P1 interacts with potential TDF-R candidates from MCF7 and BT-549 breast cells but not from HeLa or HDF-a cells. Immunofluorescence (IF) experiments identified GRP78, a TDF-R candidate, at the cell surface of MCF7, BT-549 breast cells, and HeLa cells but not HDF-a cells. IF of other HSP70 proteins demonstrated labeling on all four cell types. These results point toward GRP78 and HSP70 proteins as strong TDF-R candidates and suggest that TDF interacts with its receptor, exclusively on breast cells, through a steroid-independent pathway. 相似文献