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51.
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Christian F Szaszák M Friedl S Drewianka S Lorenz D Goncalves A Furkert J Vargas C Schmieder P Götz F Zühlke K Moutty M Göttert H Joshi M Reif B Haase H Morano I Grossmann S Klukovits A Verli J Gáspár R Noack C Bergmann M Kass R Hampel K Kashin D Genieser HG Herberg FW Willoughby D Cooper DM Baillie GS Houslay MD von Kries JP Zimmermann B Rosenthal W Klussmann E 《The Journal of biological chemistry》2011,286(11):9079-9096
A-kinase anchoring proteins (AKAPs) tether protein kinase A (PKA) and other signaling proteins to defined intracellular sites, thereby establishing compartmentalized cAMP signaling. AKAP-PKA interactions play key roles in various cellular processes, including the regulation of cardiac myocyte contractility. We discovered small molecules, 3,3'-diamino-4,4'-dihydroxydiphenylmethane (FMP-API-1) and its derivatives, which inhibit AKAP-PKA interactions in vitro and in cultured cardiac myocytes. The molecules bind to an allosteric site of regulatory subunits of PKA identifying a hitherto unrecognized region that controls AKAP-PKA interactions. FMP-API-1 also activates PKA. The net effect of FMP-API-1 is a selective interference with compartmentalized cAMP signaling. In cardiac myocytes, FMP-API-1 reveals a novel mechanism involved in terminating β-adrenoreceptor-induced cAMP synthesis. In addition, FMP-API-1 leads to an increase in contractility of cultured rat cardiac myocytes and intact hearts. Thus, FMP-API-1 represents not only a novel means to study compartmentalized cAMP/PKA signaling but, due to its effects on cardiac myocytes and intact hearts, provides the basis for a new concept in the treatment of chronic heart failure. 相似文献
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Robert Csonga Peter Ettmayer Manfred Auer Christoph Eckerskorn Jörg Eder Hannelore Klier 《FEBS letters》1996,380(3):209-214
Hypusine synthesis in the eukaryotic initiation factor 5A is a unique two-step posttranslational modification. After deoxyhypusine is generated by the deoxyhypusine synthase, the deoxyhypusine hydroxylase (EC 1.14.99.29) catalyzes the formation of mature hypusine. A rapid assay for monitoring the deoxyhypusine hydroxylase activity was established, employing the oxidative cleavage of the hypusyl residue and subsequent extraction of the generated aldehydes. As metal ion chelators have been reported to inhibit the deoxyhypusine hydroxylase, the mechanism of this inhibition and the effect of transition metal ions on the enzyme activity were investigated. A ferric ion appears to be essential for enzymatic activity, the inhibition of which is entirely attributed to the metal ion bunding capacity of the chelators. 相似文献
55.
Haase Hannelore Bartel Sabine Karczewski Peter Morano Ingo Krause Ernst-Georg 《Molecular and cellular biochemistry》1996,163(1):99-106
In canine myocardium, the -subunit of the L-type Ca2+ channel is phosphorylated by cAMP dependent protein kinase in vitro as well as in vivo (Haase et al. FEBS Lett 335: 217–222, 1993). We have assessed the identity of the -subunit as well as its in vivo phosphorylation in representative experimental groups of catecholamine-challenged canine hearts. Adrenergic stimulation by high doses of both noradrenaline and isoprenaline induced rapid (within 20 sec) and nearly complete phosphorylation of the Ca2+ channel -subunit. Phosphorylation in vivo was about 4-fold higher as compared to untreated controls. When related to catecholamine-depleted (reserpine-treated) hearts noradrenaline and isoprenaline increased the in vivo phosphorylation of the -subunit even 8-fold. This phosphorylation correlated positively with tissue levels of cAMP, endogenous particulated cAMP-dependent protein kinase (PKA) and the rate of contractile force development dP/dtmax. The results imply the involvement of a PKA-mediated phosphorylation of the Ca2+ channel -subunit in the adrenergic stimulation of intact canine myocardium. 相似文献
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TDP‐43 loss of function inhibits endosomal trafficking and alters trophic signaling in neurons
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Benjamin M Schwenk Hannelore Hartmann Alperen Serdaroglu Martin H Schludi Daniel Hornburg Felix Meissner Denise Orozco Alessio Colombo Sabina Tahirovic Meike Michaelsen Franziska Schreiber Simone Haupt Michael Peitz Oliver Brüstle Clemens Küpper Thomas Klopstock Markus Otto Albert C Ludolph Thomas Arzberger Peer‐Hendrik Kuhn Dieter Edbauer 《The EMBO journal》2016,35(21):2350-2370
58.
Clare B. O’Donovan Marianne C. Walsh Hannah Forster Clara Woolhead Carlos Celis-Morales Rosalind Fallaize Anna L. Macready Cyril F. M. Marsaux Santiago Navas-Carretero Rodrigo San-Cristobal Silvia Kolossa Christina Mavrogianni Christina P. Lambrinou George Moschonis Magdalena Godlewska Agnieszka Surwillo Jildau Bouwman Keith Grimaldi Iwona Traczyk Christian A. Drevon Hannelore Daniel Yannis Manios J. Alfredo Martinez Wim H. M. Saris Julie A. Lovegrove John C. Mathers Michael J. Gibney Lorraine Brennan Eileen R. Gibney 《Genes & nutrition》2016,11(1):25
Background
It is hypothesised that individuals with knowledge of their genetic risk are more likely to make health-promoting dietary and lifestyle changes. The present study aims to test this hypothesis using data from the Food4Me study. This was a 6-month Internet-based randomised controlled trial conducted across seven centres in Europe where individuals received either general healthy eating advice or varying levels of personalised nutrition advice. Participants who received genotype-based personalised advice were informed whether they had the risk (CT/TT) (n?=?178) or non-risk (CC) (n?=?141) alleles of the methylenetetrahydrofolate reductase (MTHFR) gene in relation to cardiovascular health and the importance of a sufficient intake of folate. General linear model analysis was used to assess changes in folate intake between the MTHFR risk, MTHFR non-risk and control groups from baseline to month 6 of the intervention.Results
There were no differences between the groups for age, gender or BMI. However, there was a significant difference in country distribution between the groups (p?=?0.010). Baseline folate intakes were 412?±?172, 391?±?190 and 410?±?186 μg per 10 MJ for the risk, non-risk and control groups, respectively. There were no significant differences between the three groups in terms of changes in folate intakes from baseline to month 6. Similarly, there were no changes in reported intake of food groups high in folate.Conclusions
These results suggest that knowledge of MTHFR 677C?→?T genotype did not improve folate intake in participants with the risk variant compared with those with the non-risk variant.Trial registration
ClinicalTrials.gov NCT0153013959.
Rodrigo San-Cristobal Santiago Navas-Carretero Fermín I. Milagro J. Ignacio Riezu-Boj Elizabeth Guruceaga Carlos Celis-Morales Katherine M. Livingstone Lorraine Brennan Julie A. Lovegrove Hannelore Daniel Wim H. Saris Iwonna Traczyk Yannis Manios Eileen R. Gibney Michael J. Gibney John C. Mathers J. Alfredo Martinez 《Journal of physiology and biochemistry》2016,73(3):465-474
Epigenetics has an important role in the regulation of metabolic adaptation to environmental modifications. In this sense, the determination of epigenetic changes in non-invasive samples during the development of metabolic diseases could play an important role in the procedures in primary healthcare practice. To help translate the knowledge of epigenetics to public health practice, the present study aims to explore the parallelism of methylation levels between white blood cells and buccal samples in relation to obesity and associated disorders. Blood and buccal swap samples were collected from a subsample of the Spanish cohort of the Food4Me study. Infinium HumanMethylation450 DNA Analysis was carried out for the determination of methylation levels. Standard deviation for β values method and concordance correlation analysis were used to select those CpG which showed best parallelism between samples. A total of 277 CpGs met the criteria and were selected for an enrichment analysis and a correlation analysis with anthropometrical and clinical parameters. From those selected CpGs, four presented high associations with BMI (cg01055691 in GAP43; r = ?0.92 and rho = ?0.84 for blood; r = ?0.89 and rho = ?0.83 for buccal sample), HOMA-IR (cg00095677 in ATP2A3; r = 0.82 and rho = ?0.84 for blood; r = ?0.8 and rho = ?0.83 for buccal sample) and leptin (cg14464133 in ADARB2; r = ?0.9182 and rho = ?0.94 for blood; r = ?0.893 and rho = ?0.79 for buccal sample). These findings demonstrate the potential application of non-invasive buccal samples in the identification of surrogate epigenetic biomarkers and identify methylation sites in GAP43, ATP2A3 and ADARB2 genes as potential targets in relation to overweight management and insulin sensibility. 相似文献
60.
Physical activity attenuates the effect of the FTO genotype on obesity traits in European adults: The Food4Me study
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![点击此处可从《Obesity (Silver Spring, Md.)》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Carlos Celis‐Morales Cyril F.M. Marsaux Katherine M. Livingstone Santiago Navas‐Carretero Rodrigo San‐Cristobal Clare B. O'donovan Hannah Forster Clara Woolhead Rosalind Fallaize Anna L. Macready Silvia Kolossa Jacqueline Hallmann Lydia Tsirigoti Christina P. Lambrinou George Moschonis Magdalena Godlewska Agnieszka Surwio Keith Grimaldi Jildau Bouwman Yannis Manios Iwona Traczyk Christian A. Drevon Laurence D. Parnell Hannelore Daniel Eileen R. Gibney Lorraine Brennan Marianne C. Walsh Mike Gibney Julie A. Lovegrove J. Alfredo Martinez Wim H.M. Saris John C. Mathers 《Obesity (Silver Spring, Md.)》2016,24(4):962-969