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81.
Amit Kaura Adam Hartley Vasileios Panoulas Ben Glampson Anoop S. V. Shah Jim Davies Abdulrahim Mulla Kerrie Woods Joe Omigie Anoop D. Shah Mark R. Thursz Paul Elliott Harry Hemmingway Bryan Williams Folkert W. Asselbergs Michael OSullivan Graham M. Lord Adam Trickey Jonathan AC Sterne Dorian O. Haskard Narbeh Melikian Darrel P. Francis Wolfgang Koenig Ajay M. Shah Rajesh Kharbanda Divaka Perera Riyaz S. Patel Keith M. Channon Jamil Mayet Ramzi Khamis 《PLoS medicine》2022,19(2)
BackgroundThere is limited evidence on the use of high-sensitivity C-reactive protein (hsCRP) as a biomarker for selecting patients for advanced cardiovascular (CV) therapies in the modern era. The prognostic value of mildly elevated hsCRP beyond troponin in a large real-world cohort of unselected patients presenting with suspected acute coronary syndrome (ACS) is unknown. We evaluated whether a mildly elevated hsCRP (up to 15 mg/L) was associated with mortality risk, beyond troponin level, in patients with suspected ACS.Methods and findingsWe conducted a retrospective cohort study based on the National Institute for Health Research Health Informatics Collaborative data of 257,948 patients with suspected ACS who had a troponin measured at 5 cardiac centres in the United Kingdom between 2010 and 2017. Patients were divided into 4 hsCRP groups (<2, 2 to 4.9, 5 to 9.9, and 10 to 15 mg/L). The main outcome measure was mortality within 3 years of index presentation. The association between hsCRP levels and all-cause mortality was assessed using multivariable Cox regression analysis adjusted for age, sex, haemoglobin, white cell count (WCC), platelet count, creatinine, and troponin.Following the exclusion criteria, there were 102,337 patients included in the analysis (hsCRP <2 mg/L (n = 38,390), 2 to 4.9 mg/L (n = 27,397), 5 to 9.9 mg/L (n = 26,957), and 10 to 15 mg/L (n = 9,593)). On multivariable Cox regression analysis, there was a positive and graded relationship between hsCRP level and mortality at baseline, which remained at 3 years (hazard ratio (HR) (95% CI) of 1.32 (1.18 to 1.48) for those with hsCRP 2.0 to 4.9 mg/L and 1.40 (1.26 to 1.57) and 2.00 (1.75 to 2.28) for those with hsCRP 5 to 9.9 mg/L and 10 to 15 mg/L, respectively. This relationship was independent of troponin in all suspected ACS patients and was further verified in those who were confirmed to have an ACS diagnosis by clinical coding. The main limitation of our study is that we did not have data on underlying cause of death; however, the exclusion of those with abnormal WCC or hsCRP levels >15 mg/L makes it unlikely that sepsis was a major contributor.ConclusionsThese multicentre, real-world data from a large cohort of patients with suspected ACS suggest that mildly elevated hsCRP (up to 15 mg/L) may be a clinically meaningful prognostic marker beyond troponin and point to its potential utility in selecting patients for novel treatments targeting inflammation.Trial registrationClinicalTrials.gov - Amit Kaura and colleagues investigate whether mildly elevated high sensitivity C-reactive protein is associated with mortality risk in patients with suspected acute coronary syndromes. NCT03507309相似文献
82.
The hypothesis that play behavior is more prevalent in larger-brained animals has recently been challenged. It may be, for
example, that only certain brain structures are related to play. Here, we analyze social play behavior with regards to the
cerebellum: a structure strongly implicated in motor-development, and possibly also in cognitive skills. We present an evolutionary
analysis of social play and the cerebellum, using a phylogenetic comparative method. Social play frequency and relative cerebellum
size are positively correlated. Hence, there appears to be a link between the evolutionary elaboration of social play and
the cerebellum.
Kerrie Lewis recently received her Ph.D. from the University of Durham, U.K., under the supervision of Robert Barton. She
is currently working in a postdoctoral position at Duke University, conducting research into primate numerical cognition.
Robert Barton is a Reader in Evolutionary Anthropology at the University of Durham. His interests comprise primate behavior
and brain evolution. Both authors are keen advocates for the use of the comparative method in evolutionary studies. 相似文献
83.
Morris R Morgan BS Lewis TM Pierce KD Pisano A Schofield PR 《Journal of neurochemistry》2004,90(6):1445-1452
We utilised the retrograde transport machinery of neurones to deliver naked plasmid DNA into the central nervous system. A 5.4-kb fragment of the glycine receptor (GlyR) alpha1 subunit gene was cloned and used to drive the expression of a construct encoding for the enhanced green fluorescent protein (EGFP). Injections of the plasmid DNA in the tongue of mice resulted in the expression of the marker protein in hypoglossal motor neurones, showing that the GlyRalpha1 promoter sequence is sufficient to drive expression of the transgene. In order to determine the specificity of expression of the 5.4-kb fragment of the GlyR alpha1 subunit gene promoter, we subsequently injected the plasmid DNA into the mouse central nucleus of the amygdala. This nucleus receives projections from the parabrachial nucleus, a brainstem area that has a high density of GlyRs, and from the insular cortex, a forebrain structure devoid of GlyRs. We observed EGFP-labelled neurones in the parabrachial nucleus, but not in the insular cortex, indicating that the 5.4-kb GlyR alpha1 subunit gene promoter confers specificity of expression. This approach provides a simple and rapid way to identify, in vivo, promoter elements that mediate neurone-specific gene expression. 相似文献
84.
Maladaptive memories that associate environmental stimuli with the effects of drugs of abuse are known to be a major cause of relapse to, and persistence of, a drug addictive habit. However, memories may be disrupted after their acquisition and consolidation by impairing their reconsolidation. Here, we show that infusion of Zif268 antisense oligodeoxynucleotides into the basolateral amygdala, prior to the reactivation of a well-learned memory for a conditioned stimulus (CS)-cocaine association, abolishes the acquired conditioned reinforcing properties of the drug-associated stimulus and thus its impact on the learning of a new cocaine-seeking response. Furthermore, we show that reconsolidation of CS-fear memories also requires Zif268 in the amygdala. These results demonstrate that appetitive CS-drug memories undergo reconsolidation in a manner similar to aversive memories and that this amygdala-dependent reconsolidation can be disrupted to reduce the impact of drug cues on drug seeking. 相似文献
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Hajime Muraguchi Kiwamu Umezawa Mai Niikura Makoto Yoshida Toshinori Kozaki Kazuo Ishii Kiyota Sakai Motoyuki Shimizu Kiyoshi Nakahori Yuichi Sakamoto Cindy Choi Chew Yee Ngan Eika Lindquist Anna Lipzen Andrew Tritt Sajeet Haridas Kerrie Barry Igor V. Grigoriev Patricia J. Pukkila 《PloS one》2015,10(10)
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89.
Zhi Li Peng Zhou Rafael Della Coletta Tifu Zhang Alex B. Brohammer Christine H. O’Connor Brieanne Vaillancourt Anna Lipzen Chris Daum Kerrie Barry Natalia de Leon Cory D. Hirsch C. Robin Buell Shawn M. Kaeppler Nathan M. Springer Candice N. Hirsch 《The Plant journal : for cell and molecular biology》2021,105(1):93-107
90.
Sucgang R Kuo A Tian X Salerno W Parikh A Feasley CL Dalin E Tu H Huang E Barry K Lindquist E Shapiro H Bruce D Schmutz J Salamov A Fey P Gaudet P Anjard C Babu MM Basu S Bushmanova Y van der Wel H Katoh-Kurasawa M Dinh C Coutinho PM Saito T Elias M Schaap P Kay RR Henrissat B Eichinger L Rivero F Putnam NH West CM Loomis WF Chisholm RL Shaulsky G Strassmann JE Queller DC Kuspa A Grigoriev IV 《Genome biology》2011,12(2):R20