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61.
Whitney E. Melroy Sarah H. Stephens Joseph T. Sakai Helen M. Kamens Matthew B. McQueen Robin P. Corley Michael C. Stallings Christian J. Hopfer Kenneth S. Krauter Sandra A. Brown John K. Hewitt Marissa A. Ehringer 《Behavior genetics》2014,44(4):356-367
Previous studies have shown associations between single nucleotide polymorphisms (SNPs) in gamma aminobutyric acid receptor alpha 2 (GABRA2) and adolescent conduct disorder (CD) and alcohol dependence in adulthood, but not adolescent alcohol dependence. The present study was intended as a replication and extension of this work, focusing on adolescent CD, adolescent alcohol abuse and dependence (AAD), and adult AAD. Family based association tests were run using Hispanics and non-Hispanic European American subjects from two independent longitudinal samples. Although the analysis provided nominal support for an association with rs9291283 and AAD in adulthood and CD in adolescence, the current study failed to replicate previous associations between two well replicated GABRA2 SNPs and CD and alcohol dependence. Overall, these results emphasize the utility of including an independent replication sample in the study design, so that the results from an individual sample can be weighted in the context of its reproducibility. 相似文献
62.
Brett C. Haberstick Andrew Smolen Gary L. Stetler Joyce W. Tabor Taylor Roy H. Rick Casey Alicia Pardo Forest Roy Lauren A. Ryals Christina Hewitt Eric A. Whitsel Carolyn T. Halpern Ley A. Killeya-Jones Jeffrey M. Lessem John K. Hewitt Kathleen Mullan Harris 《Behavior genetics》2014,44(5):487-497
Simple sequence repeats (SSRs) are one of the earliest available forms of genetic variation available for analysis and have been utilized in studies of neurological, behavioral, and health phenotypes. Although findings from these studies have been suggestive, their interpretation has been complicated by a variety of factors including, among others, limited power due to small sample sizes. The current report details the availability, diversity, and allele and genotype frequencies of six commonly examined SSRs in the ethnically diverse, population-based National Longitudinal Study of Adolescent Health. A total of 106,743 genotypes were generated across 15,140 participants that included four microsatellites and two di-nucleotide repeats in three dopamine genes (DAT1, DRD4, DRD5), the serotonin transporter, and monoamine oxidase A. Allele and genotype frequencies showed a complex pattern and differed significantly between populations. For both di-nucleotide repeats we observed a greater allelic diversity than previously reported. The availability of these six SSRs in a large, ethnically diverse sample with extensive environmental measures assessed longitudinally offers a unique resource for researchers interested in health and behavior. 相似文献
63.
Dorian G. Mitchem Alicia M. Purkey Nicholas M. Grebe Gregory Carey Christine E. Garver-Apgar Timothy C. Bates Rosalind Arden John K. Hewitt Sarah E. Medland Nicholas G. Martin Brendan P. Zietsch Matthew C. Keller 《Behavior genetics》2014,44(3):270-281
Human facial attractiveness and facial sexual dimorphism (masculinity–femininity) are important facets of mate choice and are hypothesized to honestly advertise genetic quality. However, it is unclear whether genes influencing facial attractiveness and masculinity–femininity have similar, opposing, or independent effects across sex, and the heritability of these phenotypes is poorly characterized. To investigate these issues, we assessed facial attractiveness and facial masculinity–femininity in the largest genetically informative sample (n = 1,580 same- and opposite-sex twin pairs and siblings) to assess these questions to date. The heritability was ~0.50–0.70 for attractiveness and ~0.40–0.50 for facial masculinity–femininity, indicating that, despite ostensible selection on genes influencing these traits, substantial genetic variation persists in both. Importantly, we found evidence for intralocus sexual conflict, whereby alleles that increase masculinity in males have the same effect in females. Additionally, genetic influences on attractiveness were shared across the sexes, suggesting that attractive fathers tend to have attractive daughters and attractive mothers tend to have attractive sons. 相似文献
64.
Cell physiology and molecular genetics now provide the basis for the fundamental understanding of the mechanisms involved in normal and pathological physiology, modes of drug action, and risks involved in surgical procedures. Some explanations, often involving a single mutation in a protein are straightforward (e.g. cystic fibrosis transmembrane conductance regulator (CFTR) in cystic fibrosis). Others may involve a constellation of effects (e.g. obesity) and surprisingly there still remain important areas lacking comprehensive explanation (e.g. the mode of action of general anaesthetics) or close to resolution but still lacking detail (aldosterone controlling both K and Na regulation in the kidney). The present article presents a concise summary of regulation of cell function, concentrating on the cell membrane and important organelles. Signalling and second messengers, together with the role of membrane channels and transporters constitute an important aspect of this, mediated via kinases and phosphatases. Cell volume regulation, reflecting swelling and oedema, are an important aspect of organ transplantation and brain function. 相似文献
65.
P. L. Abt C. L. Marsh T. B. Dunn W. R. Hewitt J. R. Rodrigue J. M. Ham S. Feng 《American journal of transplantation》2013,13(6):1400-1404
Solid organ transplantation is encumbered by an increasing number of waitlisted patients unrequited by the current organ supply. Preclinical models suggest that advances in deceased donor management and treatment can increase the quantity and quality of organs available for transplantation. However, the science of donor intervention and the execution of high quality, prospective, multi‐center, randomized‐controlled trials are restricted by a myriad of logistical challenges mired in regulatory and ethical ambiguity. By highlighting the obstacles to conducting research in deceased donors, this report endeavors to stimulate the creation of a multi‐disciplinary framework to facilitate the design, implementation and supervision of innovative trials that increase the quantity and/or quality of deceased donor organs. 相似文献
66.
Joan Eilstein Sébastien Grégoire Aurélie Fabre Eric Arbey Camille Géniès Hélène Duplan Helga Rothe Corie Ellison Richard Cubberley Andreas Schepky Daniela Lange Martina Klaric Nicola J. Hewitt Carine Jacques-Jamin 《Journal of applied toxicology : JAT》2020,40(3):416-433
The abundance of xenobiotic metabolizing enzymes (XMEs) is different in the skin and liver; therefore, it is important to differentiate between liver and skin metabolism when applying the information to safety assessment of topically applied ingredients in cosmetics. Here, we have employed EpiSkin™ S9 and human liver S9 to investigate the organ-specific metabolic stability of 47 cosmetic-relevant chemicals. The rank order of the metabolic rate of six chemicals in primary human hepatocytes and liver S9 matched relatively well. XME pathways in liver S9 were also present in EpiSkin S9; however, the rate of metabolism tended to be lower in the latter. It was possible to rank chemicals into low-, medium- and high-clearance chemicals and compare rates of metabolism across chemicals with similar structures. The determination of the half-life for 21 chemicals was affected by one or more factors such as spontaneous reaction with cofactors or non-specific binding, but these technical issues could be accounted for in most cases. There were seven chemicals that were metabolized by liver S9 but not by EpiSkin S9: 4-amino-3-nitrophenol, resorcinol, cinnamyl alcohol and 2-acetylaminofluorene (slowly metabolized); and cyclophosphamide, benzophenone, and 6-methylcoumarin. These data support the use of human liver and EpiSkin S9 as screening assays to indicate the liver and skin metabolic stability of a chemical and to allow for comparisons across structurally similar chemicals. Moreover, these data can be used to estimate the systemic bioavailability and clearance of chemicals applied topically, which will ultimately help with the safety assessment of cosmetics ingredients. 相似文献
67.
Dimasi DP Hewitt AW Straga T Pater J MacKinnon JR Elder JE Casey T Mackey DA Craig JE 《Clinical genetics》2007,72(3):255-260
Analysis of CYP1B1 in primary congenital glaucoma (PCG) patients from various ethnic populations indicates that allelic heterogeneity is high, and some mutations are population specific. No study has previously reported the rate or spectrum of CYP1B1 mutations in Australian PCG patients. The aim of this study is to determine the frequency of CYP1B1 mutations in our predominately Caucasian, Australian cohort of PCG cases. Thirty-seven probands were recruited from South-Eastern Australia, along with 100 normal control subjects. Genomic DNA was extracted and the coding regions of CYP1B1 analysed by direct sequencing. Sequence analysis identified 10 different CYP1B1 disease-causing variants in eight probands (21.6%). Five subjects were compound heterozygotes, two subjects heterozygous and one homozygous for CYP1B1 mutations. Three missense mutations are novel (D192Y, G329D, and P400S). None of the novel mutations identified were found in normal controls. One normal control subject was heterozygous for the previously reported CYP1B1 R368H mutation. Six previously described probable polymorphisms were also identified. Mutations in CYP1B1 account for approximately one in five PCG cases from Australia. Our data also supported the high degree of allelic heterogeneity seen in similar studies from other ethnic populations, thereby underscoring the fact that other PCG-related genes remain to be identified. 相似文献
68.
Systematic review with meta‐analysis: online psychological interventions for mental and physical health outcomes in gastrointestinal disorders including irritable bowel syndrome and inflammatory bowel disease
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I. Hanlon C. Hewitt K. Bell A. Phillips A. Mikocka‐Walus 《Alimentary pharmacology & therapeutics》2018,48(3):244-259
69.
Hewitt JA Hush JM Martin MH Herbert RD Latimer J 《The Australian journal of physiotherapy》2007,53(4):269-276
QUESTIONS: Can clinical prediction rules be derived for injured Australian workers with persistent musculoskeletal pain? Are they valid? DESIGN: Longitudinal observational study. PARTICIPANTS: 847 injured workers with persistent musculoskeletal pain undergoing rehabilitation. OUTCOME MEASURES: At baseline, 12 putative predictors were measured. At 9 weeks, short-term outcomes such as pain (visual analogue scale), activity limitation (Functional Rating Index) and work upgrade (increase in work hours or duties) were measured. At 6 months, long-term work status (working or not working) was measured. RESULTS: Data were obtained from 85% of the participants who were followed up at both 9 weeks (720 of 847) and 6 months (247 of 290). Predictors of outcome included high baseline pain and activity limitation, long duration of previous intervention, not working, non-English speaking background, and the area of pain. Accuracy was highest for clinical prediction rules predicting pain and level of activity limitation at 9 weeks (R2 = 0.67 and 0.69 respectively) and work status at 6 months (LR- = 0.24). CONCLUSION: Accurate clinical prediction rules have been derived and validated for injured workers with persistent musculoskeletal pain, predicting activity limitation, pain, and work outcomes following exercise-based rehabilitation. Further research to validate these prediction rules in other populations and to assess the effectiveness of tailoring intervention based on the estimated prognosis would be valuable. 相似文献
70.
Marinka L. F. Hol Daniel J. Indelicato Olga Slater Frederic Kolb Richard J Hewitt Juling Ong Alfred G. Becking Jenny Gains Julie Bradley Eric Sandler Mark N. Gaze Bradley Pieters Henry Mandeville Raquel Dávila Fajardo Reineke Schoot Johannes H. M. Merks Peter Hammond Ludwig E. Smeele Michael Suttie 《Pediatric blood & cancer》2023,70(8):e30412