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排序方式: 共有313条查询结果,搜索用时 31 毫秒
71.
Stesha C. Joseph Brittany A. Blackman Megan L. Kelly Mariana Phillips Michael W. Beaury Ivonne Martinez Christopher J. Parronchi Constantine Bitsaktsis Allan D. Blake David Sabatino 《Journal of peptide science》2014,20(9):736-745
The solid‐phase synthesis, structural characterization, and biological evaluation of a small library of cancer‐targeting peptides have been determined in HepG2 hepatoblastoma cells. These peptides are based on the highly specific Pep42 motif, which has been shown to target the glucose‐regulated protein 78 receptors overexpressed and exclusively localized on the cell surface of tumors. In this study, Pep42 was designed to contain varying lengths (3–12) of poly(arginine) sequences to assess their influence on peptide structure and biology. Peptides were effectively synthesized by 9‐fluorenylmethoxycarbonyl‐based solid‐phase peptide synthesis, in which the use of a poly(ethylene glycol) resin provided good yields (14–46%) and crude purities >95% as analyzed by liquid chromatography–mass spectrometry. Peptide structure and biophysical properties were investigated using circular dichroism spectroscopy. Interestingly, peptides displayed secondary structures that were contingent on solvent and length of the poly(arginine) sequences. Peptides exhibited helical and turn conformations, while retaining significant thermal stability. Structure–activity relationship studies conducted by flow cytometry and confocal microscopy revealed that the poly(arginine) derived Pep42 sequences maintained glucose‐regulated protein 78 binding on HepG2 cells while exhibiting cell translocation activity that was contingent on the length of the poly(arginine) strand. In single dose (0.15 mM) and dose‐response (0–1.5 mM) cell viability assays, peptides were found to be nontoxic in human HepG2 liver cancer cells, illustrating their potential as safe cancer‐targeting delivery agents. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd. 相似文献
72.
Jose M. Martínez-Sánchez Montse Ballbè Marcela Fu Juan C. Martín-Sánchez Mark Gottlieb Esteve Saltó Constantine I. Vardavas Richard Daynard Gregory N. Connolly Esteve Fernández 《PloS one》2014,9(12)
Background
Currently, there is an intensive debate about the regulation of the use of electronic cigarettes (e-cigarettes) in indoor places. The aim of this study was to assess the attitudes toward e-cigarette use in indoor workplaces and selected public and private venues among the general population in Barcelona (Spain) in 2013–2014.Methods
This is a cross-sectional study of a representative sample of the population of Barcelona (n = 736). The field work was conducted between May 2013 and February 2014. We computed the prevalence and the adjusted odds ratios (OR) derived from multivariable logistic regression models.Results
The awareness of e-cigarettes was 82.3%. Forty five percent of respondents did not agree with the use of e-cigarettes in public places and 52.3% in workplaces. The proportion of disapproval of the use of e-cigarettes in indoor places was higher at 71.5% for schools and 65.8% for hospitals and health care centers; while the prevalence of disapproval of e-cigarette use in homes and cars was lower (18.0% and 32.5%, respectively). Respondents who disagreed on the use of e-cigarettes in indoor workplaces were more likely to be older (OR = 1.64 and 1.97 for groups 45–64 and ≧65 years old, respectively), those with a high educational level (OR = 1.60), and never and former smokers (OR = 2.34 and 2.16, respectively). Increased scores in the Fagerström test for cigarette dependence were also related to increased support for their use.Conclusions
Based on this population based study, half of the general population of Barcelona does not support the use of e-cigarettes in indoor workplaces and public places, with the percentage reaching 65% for use in schools, hospitals and health care centers. Consequently, there is good societal support in Spain for the politicians and legislators to promote policies restricting e-cigarettes use in workplaces and public places, including hospitality venues. 相似文献73.
74.
Antonella Converso Timothy Hartingh Robert M. Garbaccio Edward Tasber Keith Rickert Mark E. Fraley Youwei Yan Constantine Kreatsoulas Steve Stirdivant Bob Drakas Eileen S. Walsh Kelly Hamilton Carolyn A. Buser Xianzhi Mao Marc T. Abrams Stephen C. Beck Weikang Tao Rob Lobell Laura Sepp-Lorenzino Joan Zugay-Murphy George D. Hartman 《Bioorganic & medicinal chemistry letters》2009,19(4):1240-1244
A high throughput screening campaign was designed to identify allosteric inhibitors of Chk1 kinase by testing compounds at high concentration. Activity was then observed at Km for ATP and at near-physiological concentrations of ATP. This strategy led to the discovery of a non-ATP competitive thioquinazolinone series which was optimized for potency and stability. An X-ray crystal structure for the complex of our best inhibitor bound to Chk1 was solved, indicating that it binds to an allosteric site ~13 Å from the ATP binding site. Preliminary data is presented for several of these compounds. 相似文献
75.
Patrick M Bossuyt Johannes B Reitsma David E Bruns Constantine A Gatsonis Paul P Glasziou Les M Irwig Jeroen G Lijmer David Moher Drummond Rennie Henrica C W de Vet 《BMJ (Clinical research ed.)》2003,326(7379):41-44
ObjectiveTo improve the accuracy and completeness of reporting of studies of diagnostic accuracy, to allow readers to assess the potential for bias in a study, and to evaluate a study''s generalisability.MethodsThe Standards for Reporting of Diagnostic Accuracy (STARD) steering committee searched the literature to identify publications on the appropriate conduct and reporting of diagnostic studies and extracted potential items into an extensive list. Researchers, editors, and members of professional organisations shortened this list during a two day consensus meeting, with the goal of developing a checklist and a generic flow diagram for studies of diagnostic accuracy.ResultsThe search for published guidelines about diagnostic research yielded 33 previously published checklists, from which we extracted a list of 75 potential items. At the consensus meeting, participants shortened the list to a 25 item checklist, by using evidence, whenever available. A prototype of a flow diagram provides information about the method of patient recruitment, the order of test execution, and the numbers of patients undergoing the test under evaluation and the reference standard, or both.ConclusionsEvaluation of research depends on complete and accurate reporting. If medical journals adopt the STARD checklist and flow diagram, the quality of reporting of studies of diagnostic accuracy should improve to the advantage of clinicians, researchers, reviewers, journals, and the public.The Standards for Reporting of Diagnostic Accuracy (STARD) steering group aims to improve the accuracy and completeness of reporting of studies of diagnostic accuracy. The group describes and explains the development of a checklist and flow diagram for authors of reports 相似文献
76.
Harriet A. Watkins Madhuri Chakravarthy Rekhati S. Abhayawardana Joseph J. Gingell Michael Garelja Meenakshi Pardamwar James M. W. R. McElhinney Alex Lathbridge Arran Constantine Paul W. R. Harris Tsz-Ying Yuen Margaret A. Brimble James Barwell David R. Poyner Michael J. Woolley Alex C. Conner Augen A. Pioszak Christopher A. Reynolds Debbie L. Hay 《The Journal of biological chemistry》2016,291(22):11657-11675
Adrenomedullin (AM) is a peptide hormone with numerous effects in the vascular systems. AM signals through the AM1 and AM2 receptors formed by the obligate heterodimerization of a G protein-coupled receptor, the calcitonin receptor-like receptor (CLR), and receptor activity-modifying proteins 2 and 3 (RAMP2 and RAMP3), respectively. These different CLR-RAMP interactions yield discrete receptor pharmacology and physiological effects. The effective design of therapeutics that target the individual AM receptors is dependent on understanding the molecular details of the effects of RAMPs on CLR. To understand the role of RAMP2 and -3 on the activation and conformation of the CLR subunit of AM receptors, we mutated 68 individual amino acids in the juxtamembrane region of CLR, a key region for activation of AM receptors, and determined the effects on cAMP signaling. Sixteen CLR mutations had differential effects between the AM1 and AM2 receptors. Accompanying this, independent molecular modeling of the full-length AM-bound AM1 and AM2 receptors predicted differences in the binding pocket and differences in the electrostatic potential of the two AM receptors. Druggability analysis indicated unique features that could be used to develop selective small molecule ligands for each receptor. The interaction of RAMP2 or RAMP3 with CLR induces conformational variation in the juxtamembrane region, yielding distinct binding pockets, probably via an allosteric mechanism. These subtype-specific differences have implications for the design of therapeutics aimed at specific AM receptors and for understanding the mechanisms by which accessory proteins affect G protein-coupled receptor function. 相似文献
77.
The meiotic stage of nondisjunction in trisomy 21: Determination by using DNA polymorphisms 总被引:3,自引:3,他引:0 下载免费PDF全文
Stylianos E. Antonarakis Michael B. Petersen Melvin G. McInnis Patricia A. Adelsberger Albert A. Schinzel Franz Binkert Constantine Pangalos Odile Raoul Susan A. Slaugenhaupt Mohamed Hafez Maimon M. Cohen Diane Roulson Stuart Schwartz Margareta Mikkelsen Lisbeth Tranebjaerg Frank Greenberg David I. Hoar Noreen L. Rudd Andrew C. Warren Caterina Metaxotou Christos Bartsocas Aravinda Chakravarti 《American journal of human genetics》1992,50(3):544-550
We have studied DNA polymorphisms at loci in the pericentromeric region on the long arm of chromosome 21 in 200 families with trisomy 21, in order to determine the meiotic origin of nondisjunction. Maintenance of heterozygosity for parental markers in the individual with trisomy 21 was interpreted as resulting from a meiosis I error, while reduction to homozygosity was attributed to a meiosis II error. Nondisjunction was paternal in 9 cases and was maternal in 188 cases, as reported earlier. Among the 188 maternal cases, nondisjunction occurred in meiosis I in 128 cases and in meiosis II in 38 cases; in 22 cases the DNA markers used were uninformative. Therefore meiosis I was responsible for 77.1% and meiosis II for 22.9% of maternal nondisjunction. Among the 9 paternal nondisjunction cases the error occurred in meiosis I in 2 cases (22.2%) and in meiosis II in 7 (77.8%) cases. Since there was no significant difference in the distribution of maternal ages between maternal I error versus maternal II error, it is unlikely that an error at a particular of maternal ages between maternal I error versus maternal II error, it is unlikely that an error at a particular meiotic stage contributes significantly to the increasing incidence of Down syndrome with advancing maternal age. Although the DNA polymorphisms used were at loci which map close to the centromere, it is likely that rare errors in meiotic-origin assignments may have occurred because of a small number of crossovers between the markers and the centromere.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
78.
79.
INCREASED AVOIDANCE OF SWIMMERS BY WILD BOTTLENOSE DOLPHINS (TURSIOPS TRUNCATUS) DUE TO LONG-TERM EXPOSURE TO SWIM-WITH-DOLPHIN TOURISM 总被引:1,自引:0,他引:1
The responses of wild, non-provisioned bottlenose dolphins ( Tursiops truncatus ) to swim attempts from commercial swim-with-dolphin tour boats were systematically observed during two research periods: 1994–1995 and 1997–1998. A total of 255 groups of dolphins was encountered during boat-based surveys and 36% ( n = 93) were exposed to at least one swim attempt. The operators' success with swim attempts, defined as at least one dolphin milling within 5 m of at least one swimmer, decreased from 48% in 1994–1995 to 34% in 1997–1998, and avoidance responses to swimmers increased from 22% to 31%. Dolphin response was found to vary according to swimmer placement. The greatest increase in avoidance occurred when swimmers were placed in the dolphins' path of travel. Based on sighting records of 266 individually identified dolphins, it was estimated that an average dolphin was exposed to 31 swim attempts per year. This level of exposure suggests that individual dolphins have, with cumulative experience, become sensitized to swim attempts. When a swim attempt was successful, on average it involved 19% of the group. Age-class differences in interaction rates showed that juveniles were significantly more likely to interact with swimmers than adults. This study highlights the importance of longitudinal studies in evaluating human impact and suggests the urgent need for similar studies of potential human impact on other toothed cetaceans. 相似文献
80.