全文获取类型
收费全文 | 174篇 |
免费 | 11篇 |
专业分类
185篇 |
出版年
2023年 | 1篇 |
2022年 | 5篇 |
2021年 | 3篇 |
2020年 | 6篇 |
2019年 | 3篇 |
2018年 | 5篇 |
2017年 | 2篇 |
2016年 | 10篇 |
2015年 | 7篇 |
2014年 | 13篇 |
2013年 | 10篇 |
2012年 | 12篇 |
2011年 | 10篇 |
2010年 | 5篇 |
2009年 | 10篇 |
2008年 | 11篇 |
2007年 | 11篇 |
2006年 | 7篇 |
2005年 | 14篇 |
2004年 | 7篇 |
2003年 | 10篇 |
2002年 | 4篇 |
2001年 | 2篇 |
2000年 | 2篇 |
1999年 | 2篇 |
1997年 | 2篇 |
1994年 | 1篇 |
1992年 | 1篇 |
1990年 | 2篇 |
1989年 | 2篇 |
1988年 | 2篇 |
1983年 | 1篇 |
1969年 | 1篇 |
1957年 | 1篇 |
排序方式: 共有185条查询结果,搜索用时 15 毫秒
1.
Richard Swartz Loyd West Iouri Boiko Anais Malpica Calum MacAulay Anita Carraro Martial Guillaud Dennis Cox Michele Follen 《Analytical cellular pathology》2003,25(4):193-200
This is a methodological study exploring the use of quantitative histopathology applied to the cervix to discriminate between normal and cancerous (consisting of adenocarcinoma and adenocarcinoma in situ) tissue samples. The goal is classifying tissue samples, which are populations of cells, from measurements on the cells. Our method uses one particular feature, the IODs-Index, to create a tissue level feature. The specific goal of this study is to find a threshold for the IODs-Index that is used to create the tissue level feature. The main statistical tool is Receiver Operating Characteristic (ROC) curve analysis. When applied to the data, our method achieved promising results with good estimated sensitivity and specificity for our data set. The optimal threshold for the IODs-Index was found to be 2.12. 相似文献
2.
Rikke Sogaard Lars Borre Thomas H. Braunstein Kenneth L. Madsen Nanna MacAulay 《The Journal of biological chemistry》2013,288(28):20195-20207
The dominant glutamate transporter isoform in the mammalian brain, GLT1, exists as at least three splice variants, GLT1a, GLT1b, and GLT1c. GLT1b interacts with the scaffold protein PICK1 (protein interacting with kinase C1), which is implicated in glutamatergic neurotransmission via its regulatory effect on trafficking of AMPA-type glutamate receptors. The 11 extreme C-terminal residues specific for the GLT1b variant are essential for its specific interaction with the PICK1 PDZ domain, but a functional consequence of this interaction has remained unresolved. To identify a functional effect of PICK1 on GLT1a or GLT1b separately, we employed the Xenopus laevis expression system. GLT1a and GLT1b displayed similar electrophysiological properties and EC50 for glutamate. Co-expressed PICK1 localized efficiently to the plasma membrane and resulted in a 5-fold enhancement of the leak current in GLT1b-expressing oocytes with only a minor effect on [3H]glutamate uptake. Three different GLT1 substrates all caused a slow TBOA-sensitive decay in the membrane current upon prolonged application, which provides support for the leak current being mediated by GLT1b itself. Leak and glutamate-evoked currents in GLT1a-expressing oocytes were unaffected by PICK1 co-expression. PKC activation down-regulated GLT1a and GLT1b activity to a similar extent, which was not affected by co-expression of PICK1. In conclusion, PICK1 may not only affect glutamatergic neurotransmission by its regulatory effect on glutamate receptors but may also affect neuronal excitability via an increased GLT1b-mediated leak current. This may be particularly relevant in pathological conditions such as amyotrophic lateral sclerosis and cerebral hypoxia, which are associated with neuronal GLT1b up-regulation. 相似文献
3.
Gitte Hedermann Christoffer Rasmus Vissing Karen Heje Nicolai Preisler Nanna Witting John Vissing 《PloS one》2016,11(1)
Introduction
Congenital myopathies (CM) often affect contractile proteins of the sarcomere, which could render patients susceptible to exercise-induced muscle damage. We investigated if exercise is safe and beneficial in patients with CM.Methods
Patients exercised on a stationary bike for 30 minutes, three times weekly, for 10 weeks at 70% of their maximal oxygen uptake (VO2max). Creatine kinase (CK) was monitored as a marker of muscle damage. VO2max, functional tests, and questionnaires evaluated efficacy.Results
Sixteen patients with CM were included in a controlled study. VO2max increased by 14% (range, 6–25%; 95% CI 7–20; p < 0.001) in the seven patients who completed training, and tended to decrease in a non-intervention group (n = 7; change -3.5%; range, -11–3%, p = 0.083). CK levels were normal and remained stable during training. Baseline Fatigue Severity Scale scores were high, 4.9 (SE 1.9), and tended to decrease (to 4.4 (SE 1.7); p = 0.08) with training. Nine patients dropped out of the training program. Fatigue was the major single reason.Conclusions
Ten weeks of endurance training is safe and improves fitness in patients with congenital myopathies. The training did not cause sarcomeric injury, even though sarcomeric function is affected by the genetic abnormalities in most patients with CM. Severe fatigue, which characterizes patients with CM, is a limiting factor for initiating training in CM, but tends to improve in those who train.Trial Registration
The Regional Committee on Health Research Ethics of the Capital Region of Denmark H-2-2013-066 and ClinicalTrials.gov H2-2013-066 相似文献4.
Skals Marianne Greve Anne-Sofie Fagerberg Steen K. Johnsen Nanna Christensen Mette G. Praetorius Helle A. 《Purinergic signalling》2019,15(2):265-276
Purinergic Signalling - Urosepsis is a severe condition often caused by Escherichia coli that spontaneously have ascended the urinary tract to the kidneys causing pyelonephritis and potentially... 相似文献
5.
6.
Nanna Alho Tuula Klaavuniemi Jari Ylänne Perttu Permi Sampo Mattila 《Biomolecular NMR assignments》2007,1(1):85-87
Earlier reports have shown that ALP has an internal interaction site. We were able to stablize the structure of this unfolded
part to a great extent by aspartic acid, which allowed the backbone assignment. No secondary structure of the polypeptide
was observed. 相似文献
7.
The plant plasma membrane (PM) H+-ATPase is an essential enzyme controlling plant growth and development. It is an important factor in response to abiotic and biotic stresses and is subject to tight regulation. We are in demand for new sustainable natural growth regulators and as a key enzyme for regulation of transport into the plant cell the PM H+-ATPase is a potential target for these. In this review, we have evaluated the known non-protein natural compounds with regulatory effects on the PM H+-ATPase, focusing on their mechanism of action and their potential as biologicals/growth regulators in plant production of future sustainable agriculture. 相似文献
8.
Savinko T Lauerma A Lehtimäki S Gombert M Majuri ML Fyhrquist-Vanni N Dieu-Nosjean MC Kemeny L Wolff H Homey B Alenius H 《Journal of immunology (Baltimore, Md. : 1950)》2005,175(12):8320-8326
Patients with atopic dermatitis (AD) have repeated cutaneous exposure to both environmental allergens and superantigen-producing strains of Staphylococcus aureus. We used a murine model of AD to investigate the role of staphylococcal enterotoxin B (SEB) in the modulation of allergen-induced skin inflammation. Mice were topically exposed to SEB, OVA, a combination of OVA and SEB (OVA/SEB), or PBS. Topical SEB and OVA/SEB exposure induced epidermal accumulation of CD8+ T cells and TCRVbeta8+ cells in contrast to OVA application, which induced a mainly dermal infiltration of CD4+ cells. SEB and OVA/SEB exposure elicited a mixed Th1/Th2-associated cytokine and chemokine expression profile within the skin. Restimulation of lymph node cells from OVA- and OVA/SEB-exposed mice with OVA elicited strong production of IL-13 protein, whereas substantial amounts of IFN-gamma protein were detected after SEB stimulation of cells derived from SEB- or OVA/SEB-exposed mice. Topical SEB treatment elicited vigorous production of SEB-specific IgE and IgG2a Abs and significantly increased the production of OVA-specific IgE and IgG2a Abs. The present study shows that topical exposure to SEB provokes epidermal accumulation of CD8+ T cells, a mixed Th2/Th1 type dermatitis and vigorous production of specific IgE and IgG2a Abs, which can be related to the chronic phase of atopic skin inflammation. 相似文献
9.
Nanna M Jensen Trine Dalsgaard Maria Jakobsen Roni R Nielsen Charlotte B Sørensen Lars Bolund Thomas G Jensen 《Journal of biomedical science》2011,18(1):10
Transfer of full-length genes including regulatory elements has been the preferred gene therapy strategy for clinical applications.
However, with significant drawbacks emerging, targeted gene alteration (TGA) has recently become a promising alternative to
this method. By means of TGA, endogenous DNA repair pathways of the cell are activated leading to specific genetic correction
of single-base mutations in the genome. This strategy can be implemented using single-stranded oligodeoxyribonucleotides (ssODNs),
small DNA fragments (SDFs), triplex-forming oligonucleotides (TFOs), adeno-associated virus vectors (AAVs) and zinc-finger
nucleases (ZFNs). Despite difficulties in the use of TGA, including lack of knowledge on the repair mechanisms stimulated
by the individual methods, the field holds great promise for the future. The objective of this review is to summarize and
evaluate the different methods that exist within this particular area of human gene therapy research. 相似文献
10.
Nanna Petersen Peter Ödman Albert E. Cervera Padrell Stuart Stocks Anna Eliasson Lantz Krist V. Gernaey 《Biotechnology progress》2010,26(1):263-271
There are many challenges associated with in situ collection of near infrared (NIR) spectra in a fermentation broth, particularly for highly aerated and agitated fermentations with filamentous organisms. In this study, antibiotic fermentation by the filamentous bacterium Streptomyces coelicolor was used as a model process. Partial least squares (PLS) regression models were calibrated for glucose and ammonium based on NIR spectra collected in situ. To ensure that the models were calibrated based on analyte‐specific information, semisynthetic samples were used for model calibration in addition to data from standard batches. Thereby, part of the inherent correlation between the analytes could be eliminated. The set of semisynthetic samples were generated from fermentation broth from five separate fermentations to which different amounts of glucose, ammonium, and biomass were added. This method has previously been used off line but never before in situ. The use of semisynthetic samples along with validation on an independent batch provided a critical and realistic evaluation of analyte‐specific models based on in situ NIR spectroscopy. The prediction of glucose was highly satisfactory resulting in a RMSEP of 1.1 g/L. The prediction of ammonium based on NIR spectra collected in situ was not satisfactory. A comparison with models calibrated based on NIR spectra collected off line suggested that this is caused by signal attenuation in the optical fibers in the region above 2,000 nm; a region which contains important absorption bands for ammonium. For improved predictions of ammonium in situ, it is suggested to focus efforts on enhancing the signal in that particular region. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2010 相似文献