全文获取类型
收费全文 | 121篇 |
免费 | 9篇 |
出版年
2021年 | 1篇 |
2020年 | 2篇 |
2019年 | 2篇 |
2018年 | 1篇 |
2016年 | 2篇 |
2015年 | 3篇 |
2014年 | 7篇 |
2013年 | 5篇 |
2012年 | 3篇 |
2011年 | 7篇 |
2009年 | 2篇 |
2008年 | 10篇 |
2007年 | 4篇 |
2006年 | 2篇 |
2005年 | 4篇 |
2004年 | 6篇 |
2003年 | 5篇 |
2002年 | 3篇 |
2001年 | 3篇 |
2000年 | 4篇 |
1999年 | 6篇 |
1998年 | 4篇 |
1997年 | 2篇 |
1996年 | 2篇 |
1995年 | 4篇 |
1994年 | 3篇 |
1992年 | 1篇 |
1991年 | 2篇 |
1990年 | 1篇 |
1989年 | 3篇 |
1986年 | 3篇 |
1984年 | 3篇 |
1982年 | 1篇 |
1981年 | 1篇 |
1979年 | 2篇 |
1978年 | 1篇 |
1977年 | 1篇 |
1975年 | 1篇 |
1973年 | 1篇 |
1965年 | 1篇 |
1963年 | 2篇 |
1962年 | 1篇 |
1948年 | 1篇 |
1936年 | 3篇 |
1930年 | 1篇 |
1912年 | 1篇 |
1911年 | 2篇 |
排序方式: 共有130条查询结果,搜索用时 15 毫秒
41.
Kate L E Phillips Neil Chiverton Anthony LR Michael Ashley A Cole Lee M Breakwell Gail Haddock Rowena AD Bunning Alison K Cross Christine L Le Maitre 《Arthritis research & therapy》2013,15(6):R213
Introduction
The aims of these studies were to identify the cytokine and chemokine expression profile of nucleus pulposus (NP) cells and to determine the relationships between NP cell cytokine and chemokine production and the characteristic tissue changes seen during intervertebral disc (IVD) degeneration.Methods
Real-time q-PCR cDNA Low Density Array (LDA) was used to investigate the expression of 91 cytokine and chemokine associated genes in NP cells from degenerate human IVDs. Further real-time q-PCR was used to investigate 30 selected cytokine and chemokine associated genes in NP cells from non-degenerate and degenerate IVDs and those from IVDs with immune cell infiltrates (‘infiltrated’). Immunohistochemistry (IHC) was performed for four selected cytokines and chemokines to confirm and localize protein expression in human NP tissue samples.Results
LDA identified the expression of numerous cytokine and chemokine associated genes including 15 novel cytokines and chemokines. Further q-PCR gene expression studies identified differential expression patterns in NP cells derived from non-degenerate, degenerate and infiltrated IVDs. IHC confirmed NP cells as a source of IL-16, CCL2, CCL7 and CXCL8 and that protein expression of CCL2, CCL7 and CXCL8 increases concordant with histological degenerative tissue changes.Conclusions
Our data indicates that NP cells are a source of cytokines and chemokines within the IVD and that these expression patterns are altered in IVD pathology. These findings may be important for the correct assessment of the ‘degenerate niche’ prior to autologous or allogeneic cell transplantation for biological therapy of the degenerate IVD. 相似文献42.
Vincent EJ Jassey Geneviève Chiapusio Philippe Binet Alexandre Buttler Fatima Laggoun‐Défarge Frédéric Delarue Nadine Bernard Edward AD Mitchell Marie‐Laure Toussaint André‐Jean Francez Daniel Gilbert 《Global Change Biology》2013,19(3):811-823
Peatlands contain approximately one third of all soil organic carbon (SOC). Warming can alter above‐ and belowground linkages that regulate soil organic carbon dynamics and C‐balance in peatlands. Here we examine the multiyear impact of in situ experimental warming on the microbial food web, vegetation, and their feedbacks with soil chemistry. We provide evidence of both positive and negative impacts of warming on specific microbial functional groups, leading to destabilization of the microbial food web. We observed a strong reduction (70%) in the biomass of top‐predators (testate amoebae) in warmed plots. Such a loss caused a shortening of microbial food chains, which in turn stimulated microbial activity, leading to slight increases in levels of nutrients and labile C in water. We further show that warming altered the regulatory role of Sphagnum‐polyphenols on microbial community structure with a potential inhibition of top predators. In addition, warming caused a decrease in Sphagnum cover and an increase in vascular plant cover. Using structural equation modelling, we show that changes in the microbial food web affected the relationships between plants, soil water chemistry, and microbial communities. These results suggest that warming will destabilize C and nutrient recycling of peatlands via changes in above‐ and belowground linkages, and therefore, the microbial food web associated with mosses will feedback positively to global warming by destabilizing the carbon cycle. This study confirms that microbial food webs thus constitute a key element in the functioning of peatland ecosystems. Their study can help understand how mosses, as ecosystem engineers, tightly regulate biogeochemical cycling and climate feedback in peatlands 相似文献
43.
Morten Nilsen Asima Lokmic Inga Leena Angell Karin C. Ldrup Carlsen Kai-Hkon Carlsen Guttorm Haugen Gunilla Hedlin Christine Monceyron Jonassen Benjamin J. Marsland Bjrn Nordlund Eva Maria Rehbinder Carina Madelen Saunders Hvard O. Skjerven Lars Snipen Anne Cathrine Staff Cilla Sderhll Riyas Vettukattil Knut Rudi 《Applied and environmental microbiology》2021,87(6)
44.
Afiniki B Zarafi AM Emechebe AD Akpa O Alabi 《Archives Of Phytopathology And Plant Protection》2013,46(1):11-17
The effect of various levels of nitrogen (0.0, 30.0, 60.0, 120.0) and phosphorus (0.0, 6.5, 13.0, 36.0) on the incidence and severity of downy mildew of pearl millet and yield of two pearl millet varieties (Zango and GB8375) were studied under field conditions in 2000 and 2001 respectively. Both nitrogen and phosphorus significantly increased incidence and severity of the disease in the two varieties. Grain yield and 1000 grain weight of the varieties also increased with nitrogen and phosphorus levels. 相似文献
45.
46.
N-4-Pyrimidinyl-1H-indazol-4-amine inhibitors of Lck: indazoles as phenol isosteres with improved pharmacokinetics 总被引:1,自引:0,他引:1
Bamborough P Angell RM Bhamra I Brown D Bull J Christopher JA Cooper AW Fazal LH Giordano I Hind L Patel VK Ranshaw LE Sims MJ Skone PA Smith KJ Vickerstaff E Washington M 《Bioorganic & medicinal chemistry letters》2007,17(15):4363-4368
2,4-Dianilino pyrimidines are well-known inhibitors of tyrosine kinases including lymphocyte specific kinase (Lck). Structure-activity relationships at the 4-position are discussed and rationalised. Examples bearing a 2-methyl-5-hydroxyaniline substituent at the 4-position were especially potent but showed poor oral pharmacokinetics. Replacement of this substituent by 4-amino(5-methyl-1H-indazole) yielded compounds with comparable enzyme potency and improved pharmacokinetic properties. 相似文献
47.
To evaluate the quantitative and qualitative changes in amino acids related to internal nitrogen content and growth rate of Ulva ohnoi, the supply of nitrogen to outdoor cultures of the seaweed was manipulated by simultaneously varying water nitrogen concentrations and renewal rate. Both internal nitrogen content and growth rate varied substantially, and the quantitative and qualitative changes in amino acids were described in the context of three internal nitrogen states: nitrogen‐limited, metabolic, and luxury. The nitrogen limited state was defined by increases in all amino acids with increasing nitrogen content and growth up until 1.2% internal nitrogen. The metabolic nitrogen state was defined by increases in all amino acids with increasing internal nitrogen content up to 2.6%, with no increases in growth rate. Luxury state was defined by internal nitrogen content above 2.6%, which occurred only when nitrogen availability was high but growth rates were reduced. In this luxury circumstance, excess nitrogen was accumulated as free amino acids, in two phases. The first phase was distinguished by a small increase in the majority of amino acids up to ≈3.3% internal nitrogen, and the second by a large increase in glutamic acid, glutamine, and arginine up to 4.2% internal nitrogen. These results demonstrate that the relationship between internal nitrogen content and amino acid quality is dynamic but predictable, and could be used for the selective culture of seaweeds. 相似文献
48.
Sebastian M. Lambert David R. Langley James A. Garnett Richard Angell Katy Hedgethorne Nicholas A. Meanwell Steve J. Matthews 《Protein science : a publication of the Protein Society》2014,23(6):723-734
New direct acting antivirals (DAAs) such as daclatasvir (DCV; BMS‐790052), which target NS5A function with picomolar potency, are showing promise in clinical trials. The exact nature of how these compounds have an inhibitory effect on HCV is unknown; however, major resistance mutations appear in the N‐terminal region of NS5A that include the amphipathic helix and domain 1. The dimeric symmetry of these compounds suggests that they act on a dimer of NS5A, which is also consistent with the presence of dimers in crystals of NS5A domain 1 from genotype 1b. Genotype 1a HCV is less potently affected by these compounds and resistance mutations have a greater effect than in the 1b genotypes. We have obtained crystals of domain 1 of the important 1a NS5A homologue and intriguingly, our X‐ray crystal structure reveals two new dimeric forms of this domain. Furthermore, the high solvent content (75%) makes it ideal for ligand‐soaking. Daclatasvir (DCV) shows twofold symmetry suggesting NS5A dimers may be of physiological importance and serve as potential binding sites for DCV. These dimers also allow for new conformations of a NS5A expansive network which could explain its operation on the membranous web. Additionally, sulfates bound in the crystal structure may provide evidence for the previously proposed RNA binding groove, or explain regulation of NS5A domain 2 and 3 function and phosphorylation, by domain 1. 相似文献
49.
50.