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41.
SIRT1/HERC4 Locus Associated With Bisphosphonate‐Induced Osteonecrosis of the Jaw: An Exome‐Wide Association Analysis
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Joseph Katz Alberto Riva Peter Lakatos Bernadett Balla Janos Kosa Mihaly Vaszilko Gian Andrea Pelliccioni Noa Davis Taimour Y Langaee Jan S Moreb Yan Gong 《Journal of bone and mineral research》2018,33(1):91-98
Osteonecrosis of the jaw (ONJ) is a rare, but serious drug side effect, mainly associated with the use of intravenous (iv) bisphosphonates (BPs). The purpose of this study was to identify genetic variants associated with ONJ in patients of European ancestry treated with iv BPs using whole‐exome sequencing (WES). The WES phase 1 included 44 multiple myeloma patients (22 ONJ cases and 22 controls) and WES phase 2 included 17 ONJ patients with solid tumors. Multivariable logistic regression analysis was performed to estimate the odds ratios (ORs) and 95% confidence intervals (CI), adjusting for age, sex, and principal components for ancestry. Meta‐analysis of WES phase 1 and 2 was performed to estimate the combined ORs. In silico analyses were then performed to identify expression quantitative loci (eQTL) single‐nucleotide polymorphisms (SNPs) that are in high linkage disequilibrium (LD) with the top SNPs. The associations of the potentially functional SNPs were replicated and validated in an independent case‐control study of 48 patients of European ancestry treated with iv BPs (19 ONJ cases and 29 controls). The top SNPs in the exome‐wide association meta‐analysis were two SNPs on chromosome 10: SIRT1 SNP rs7896005 and HERC4 SNP rs3758392 with identical OR of 0.07 (0.01–0.46; p = 3.83 × 10?5). In the in silico functional analyses, two promoter region SNPs (rs7894483 and rs3758391) were identified to be in high LD with the index SNPs and are eQTLs for SIRT1 gene in whole blood in the GTEx database. The ORs were 0.30 (0.10–0.88), 0.26 (0.12–0.55), and 0.26 (0.12–0.55) for the WES top SNP rs7896005 and two promoter SNPs rs7894483 and rs3758391, respectively, in the replication sample. In summary, we identified the SIRT1/HERC4 locus on chromosome 10 to be associated with iv BP‐induced ONJ and two promoter SNPs that might be the potential genetic markers for this association. © 2017 The Authors.Journal of Bone and Mineral Research Published by Wiley Periodicals Inc. 相似文献
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43.
One year oral Toxicity of D-004, a lipid extract from Roystonea regia fruits, in Sprague Dawley rats
A. Gutiérrez R. Gámez M. Noa R. Mas D. Arencibia B. Pardo M. Valle A. Oyarzábal D. Curveco H. García E. Goicochea N. Mendoza S. Jiménez. 《Food and chemical toxicology》2011,49(11):2855-2861
D-004, a lipid extract of royal palm (Roystonea regia) fruits that contains a reproducible mixture of fatty acids, has been shown to prevent testosterone and phenylephrine-induced prostate hyperplasia in rodents. This study investigated the long-term oral toxicity of D-004 in rats. Rats from both sexes were randomized into four groups (20 rats sex/group): a control and three treated with D-004 (800, 1500 or 2000 mg/kg/day, respectively). At study completion, rats were sacrificed under anaesthesia. Determinations of blood biochemical and haematological parameters and organ weight were done. Also, necropsy and histopathological studies were performed. Four of 160 rats died before study completion. No clinical signs of toxicity were observed throughout the study. Food and water consumption, bodyweight, blood biochemical and haematological parameters, organ weight ratios and histopathological findings were similar in control and treated groups. The histological lesions found in treated animals are commonly present in this specie and strain according to literature and our historical data. In conclusion, long-term (12 months) oral treatment of rats with D-004 (800–2000 mg/kg/day) did not show evidences of D-004-related toxicity under our conditions. The highest dose tested (2000 mg/kg) was a no-observed adverse effect level in this study. 相似文献
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45.
Valevski A Gilat Y Olfson M Benaroya-Milshtein N Weizman A 《International clinical psychopharmacology》2012,27(3):159-164
This study assessed the relationship between pharmacological regimens at hospital discharge and hospital readmission among schizophrenia patients. The records reviewed were all consecutive admissions (N=720) from a specific catchment area during the period 1991-2005. Two main groups were selected for analysis: the first group (N=537) included patients discharged with first-generation antipsychotics (FGA), and the second group (N=183) included patients with second-generation antipsychotics (SGA). Data on clinical and demographic characteristics at discharge, including a brief psychiatric rating scale and pharmacological treatment, were collected. The rate of readmission within 12 months was analyzed in relation to the specific pharmacological treatment at discharge. There was no significant difference in the risk of readmission in patients treated with SGA compared with FGA. Adjuvant psychotropic medications to either FGA or SGA did not attenuate the risk of readmission. The readmission rate in patients treated with clozapine (N=74) was significantly lower in comparison with depot FGA (N=293) medications (P=0.016). There was no advantage of SGA over FGA, with or without adjuvant psychotropic treatment, with regard to rehospitalization risk during the 12-month follow-up. Clozapine was found to reduce the risk for readmission in comparison with depot FGA. 相似文献
46.
Susan G. Forman S. Serene Olin Kimberly Eaton Hoagwood Maura Crowe Noa Saka 《School mental health》2009,1(1):26-36
This study examined the factors that are important to successful implementation and sustainability of evidence-based interventions
in school settings. Developers of interventions that have been designated as “evidence-based” in multiple vetted lists and
registries available to schools participated in a structured interview. The interview focused on potential facilitators and
barriers to implementation and sustainability of their intervention. The interviews were transcribed and coded to identify
similarities and differences among the responses as well as themes that cut across participants. Results indicated that those
concerned with effective implementation and sustainability need to address several areas: (a) development of principal and
other administrator support; (b) development of teacher support; (c) development of financial resources to sustain practice;
(d) provision of high-quality training and consultation to ensure fidelity; (e) alignment of the intervention with school
philosophy, goals, policies, and programs; (f) ensuring that program outcomes and impact are visible to key stakeholders;
and (g) development of methods for addressing turnover in school staff and administrators. 相似文献
47.
Sharon Elad Moshe J. Gomori Noa Ben-Ami Silvina Friedlander-Barenboim Eran Regev Towy S. Lazarovici Noam Yarom 《Clinical oral investigations》2010,14(1):43-50
The aim of this study was to correlate clinical and computerized tomography (CT) features of bisphosphonate-related osteonecrosis of the jaws (BRONJ). All ONJ patients for whom there was complete CT scan imaging were eligible. Selected clinical parameters retrieved from their medical records were analyzed for correlation with CT parameters. The clinical presentation of BRONJ was supported by findings in CT imaging in 78.3%. The lesion’s size on CT correlated with the presence of purulent secretion (p?=?0.03). When sequestrum was present, the median lesion’s size on CT was relatively big (28 mm, range 21–43 mm). The mandibular canal cortex was never breached. CT has reasonable detection competence for diagnosing BRONJ. Purulent secretion indicates the likelihood that a more extensive involvement will be displayed on CT. A large lesion on CT should raise the index of suspicion for sequestrum. The CT appearance of a continuous cortex of the mandibular canal may serve as a differential parameter between BRONJ and metastasis to the jaw. 相似文献
48.
Kika G Izumi S Mori A Murano T Suzuki T Cai LY Nakamura E Goya K Maeda H Uchida N Shida M 《The Tokai journal of experimental and clinical medicine》2009,34(3):92-98
To improve the quality of life of elderly people in Japanese society where women have the longest life expectancy in the world, osteoporosis, and hyperlipidemia are among the major targets of medical treatment. To differentiate two types of regimens for hormone replacement therapy (HRT), we tried to evaluate the efficacy on lipid and bone metabolism. With informed consent, 34 postmenopausal women of more than 2 years were assigned to receive 1 of 2 types of HRT (the HRT group) for 12 months observation: one with a combination of conjugated equine estrogen (CEE) 0.625 mg/day and medroxyprogesterone acetate (MPA) 2.5 mg/day (the CEE group), and the other with oral estriol (E3) 2 mg/day (the E3 group). Parameters of serum lipid were measured, as well as those of bone metabolism with bone mineral density (BMD) by dual-energy X-ray absorptiometry (DEXA) using QDR-2000. In HRT groups, lipid and bone metabolism were confirmed to be improved. Whereas, an increase of triglycerides (TG) observed in the CEE group was not observed in the E3 group. Thus, in the clinical management of postmenopausal women, oral E3 preparation as an alternative regimen for HRT for CEE might be efficacious. 相似文献
49.
Goldman M Rosenfeld-Yehoshua N Lerner-Geva L Lazarovitch T Schwartz D Grisaru-Soen G 《Pediatric nephrology (Berlin, Germany)》2008,23(5):765-768
This retrospective chart review sought to determine clinical, radiological, and gender-associated characteristics of community-acquired
Pseudomonas aeruginosa (PA) urinary tract infections (UTIs) among children admitted to two medical centers. The records of 73 children with community-acquired
PA UTIs were compared with records of 109 children with community-acquired UTIs caused by other pathogens. The mean age of
both groups was similar. The PA UTI group included more boys. Features significantly more common in the PA UTI group were
the number of patients who had undergone urinary tract surgery, patients with skeletal and/or neurological malformation, patients
with >1 previous episode of UTI, patients on prophylactic antibiotic treatment on admission, and patients with pathological
renal ultrasound and voiding cystourethrography (VCUG) findings. Multivariate logistic regression analysis revealed the following
to be associated with PA UTI: >1 episode of UTI in the past [odds ratio (OR) = 35.5; 95% confidence interval (CI) 11.6–108.7],
previous urinary tract surgery (OR = 34.1; 95% CI 7.00–166.2), and pathological VCUG results (OR = 2.62; 95% CI 0.96–7.15).
In conclusion, PA UTI is associated with >1 previous UTI, urinary tract abnormalities, and past urinary tract surgery. We
recommend that when UTI is suspected in children with these risk factors, a thorough radiologic investigation, including a
VCUG, should be considered.
Drs. Goldman and Rosenfeld-Yehoshua contributed equally to this work. 相似文献
50.
Among terrestrial mammals, elephants share the unique status, along with humans and great apes, of having large brains, being long-lived and having offspring that require long periods of dependency. Elephants have the largest brains of all terrestrial mammals, including the greatest volume of cerebral cortex. In contrast to what one might expect from such a large-brained species, the performance of elephants in cognitive feats, such as tool use, visual discrimination learning and tests of "insight" behavior, is unimpressive in comparison to the performance by chimpanzees and, of course, humans. Where elephants do seem to excel is in long-term, extensive spatial-temporal and social memory. In addition, elephants appear to be somewhat unique among non-human species in their reactions to disabled and deceased conspecifics, exhibiting behaviors that are mindful of "theory-of-mind" phenomena. Information gleaned from studies on the neural cytoarchitecture of large brains reveals that the neurons of the cerebral cortex of elephants are much less densely populated than in large-brained primates. The interactions between cortical neurons would appear to be more global and less compartmentalized into local areas, and cortical information processing slower, than in great apes and humans. Although focused neural cytoarchitecture studies on the elephant are needed, this comparative perspective on the cortical neural cytoarchitecture appears to relate to differences in behavior between elephants and their primate counterparts. 相似文献