全文获取类型
收费全文 | 679篇 |
免费 | 34篇 |
国内免费 | 5篇 |
专业分类
耳鼻咽喉 | 8篇 |
儿科学 | 16篇 |
妇产科学 | 8篇 |
基础医学 | 84篇 |
口腔科学 | 23篇 |
临床医学 | 65篇 |
内科学 | 168篇 |
皮肤病学 | 25篇 |
神经病学 | 38篇 |
特种医学 | 20篇 |
外科学 | 121篇 |
综合类 | 2篇 |
预防医学 | 51篇 |
眼科学 | 7篇 |
药学 | 43篇 |
肿瘤学 | 39篇 |
出版年
2024年 | 1篇 |
2023年 | 4篇 |
2022年 | 24篇 |
2021年 | 30篇 |
2020年 | 19篇 |
2019年 | 23篇 |
2018年 | 32篇 |
2017年 | 18篇 |
2016年 | 21篇 |
2015年 | 28篇 |
2014年 | 36篇 |
2013年 | 32篇 |
2012年 | 53篇 |
2011年 | 51篇 |
2010年 | 38篇 |
2009年 | 27篇 |
2008年 | 56篇 |
2007年 | 46篇 |
2006年 | 34篇 |
2005年 | 27篇 |
2004年 | 24篇 |
2003年 | 10篇 |
2002年 | 18篇 |
2001年 | 11篇 |
2000年 | 8篇 |
1999年 | 9篇 |
1998年 | 1篇 |
1997年 | 1篇 |
1996年 | 1篇 |
1995年 | 2篇 |
1993年 | 2篇 |
1992年 | 2篇 |
1990年 | 1篇 |
1989年 | 1篇 |
1988年 | 2篇 |
1987年 | 4篇 |
1986年 | 1篇 |
1983年 | 1篇 |
1979年 | 2篇 |
1978年 | 1篇 |
1977年 | 3篇 |
1974年 | 4篇 |
1973年 | 4篇 |
1972年 | 1篇 |
1971年 | 1篇 |
1969年 | 3篇 |
排序方式: 共有718条查询结果,搜索用时 31 毫秒
1.
2.
N Deb-Joardar N Germain G Thuret A -F Garcin P Manoli A Defreyn P Gain B Estour 《Diabetic medicine》2007,24(3):303-307
AIMS: Screening for diabetic retinopathy (DR) is highly inadequate in France because of insufficient infrastructure and increasing disease prevalence. We describe the results of the first systematic DR screening programme established in a university diabetes department. METHODS: In this cross-sectional study conducted over 1 year, consecutive adult patients underwent three-field retinal photography with the Topcon TRC NW6S digital fundus camera following pupillary dilatation with Tropicamide 1%. A questionnaire provided information on patients' systemic and ocular history. Glycated haemoglobin (HbA1c) was measured at the screening visit.Two ophthalmologists graded the retinal photographs in a masked fashion. RESULTS: Of 1157 patients attending the diabetes department, 1153 (99.7%)underwent photographic screening. Images were gradable in 96% patients.Diabetic retinopathy was detected in 522 (45%) patients and sight-threatening DR in 167 (14%). Of 704 (61%) patients previously believed to have no DR,254 (34%) screened positive. The presence of DR was associated with age,insulin use and non-Caucasian ethnicity in Type 2 patients, and with duration of diabetes and HbA1c in Type 1 and Type 2 patients. Associated ocular pathologies were diagnosed in 612 (53%) patients. CONCLUSIONS: Our photographic screening programme using pharmacological mydriasis provided a high screening coverage feasible in a hospital setting. We obtained information regarding prevalence and associated risk factors of DR inpatients attending a tertiary care centre. Screening was well accepted by patients and met with no protest from city ophthalmologists. It generated considerable interest among endocrinologists and feedback of results is expected to improve optimization of glycaemic control. 相似文献
3.
Marc Bischof MD Jürgen Debus Klaus Herfarth Thomas Muley Jutta Kappes Konstantina Storz Hans Hoffmann 《Strahlentherapie und Onkologie》2007,183(12):679-684
PURPOSE: To analyze the effectiveness of surgery and chemotherapy with or without radiotherapy in the management of limited small cell lung cancer (LSCLC) in stages I and II. PATIENTS AND METHODS: 39 patients (median age 62 years) with LSCLC in stages pT1 or pT2 and pN0 or pN1 (stages IA-IIB) who had a tumor resection and systematic lymph node dissection were reviewed retrospectively. The median follow-up period was 29 months. 35 patients (90%) received a median of four cycles of a platinum-containing chemotherapy postoperatively. 16 patients (41%) received an adjuvant thoracic radiotherapy (TRT, median 50 Gy); 21 patients (54%) received a prophylactic cranial irradiation (PCI, median 30 Gy). RESULTS: The median overall survival for all patients was 47 months, resulting in actuarial 1-, 3-, and 5-year survival rates of 97%, 58%, and 49%, respectively. Distant metastases were found in 13 patients (33%) after a median of 16 months. Patients who received an adjuvant TRT showed a trend toward improved thoracic recurrence-free survival (p = 0.06) and improved overall survival (p = 0.07) compared to those treated with surgery and chemotherapy only. Brain metastasis-free survival (p = 0.01) and overall survival (p = 0.01) were improved significantly in patients who received a PCI. CONCLUSION: Surgical tumor resection may be considered for carefully selected patients. Adjuvant chemotherapy and PCI are recommended for all patients. Adjuvant TRT is currently used in patients with positive lymph nodes (pN1), because the probability of a subclinical involvement of the mediastinal lymphatic system appears to be increased in these patients. 相似文献
4.
Hodgkin's disease of the mediastinum presented as a sternal mass in two young adults. The original biopsy materials were incorrectly interpreted as eosinophilic granuloma of bone (histiocytosis X). A delayed diagnosis (15 months) resulted in the death of one patient, whereas the other patient, whose diagnosis was made in one week, had an excellent response to therapy. 相似文献
5.
Andrew Wong Christa Lese Martin Konstantina Heretis Teresa Ruffalo Kim Wilber Walter King David H Ledbetter 《Genetics in medicine》2005,7(4):264-271
PURPOSE: Genome-wide telomere screening by fluorescence in situ hybridization (FISH) has revealed that approximately 6% of unexplained mental retardation is due to submicroscopic telomere imbalances. However, the use of FISH for telomere screening is labor intensive and time consuming, given that 41 telomeres are interrogated. We have evaluated the use of array-based Comparative Genomic Hybridization (aCGH) as a more efficient tool for identifying telomere rearrangements. METHODS: In this study, 102 individuals with unexplained mental retardation, with either normal or abnormal FISH results, were selected for a blinded retrospective study using aCGH. Results between the two methodologies were compared to ascertain the ability of aCGH to be used in a clinical diagnostics setting. RESULTS: We detected 100% of all imbalances previously identified by FISH (n = 17) and identified two additional abnormalities, a 10q telomere duplication and an interstitial duplication of 22q11. Interphase FISH analysis verified all abnormal array results. We also demonstrated that aCGH can accurately calibrate the size of telomere imbalances by using an array with "molecular rulers" for the telomeric regions of 1p, 16p, 17p, and 22q. CONCLUSION: This study demonstrates that aCGH is an equivalent methodology to telomere FISH for detecting submicroscopic deletions. In addition, small duplications that are not easily visible by FISH can be accurately detected using aCGH. Because aCGH allows simultaneous interrogation of hundreds to thousands of DNA probes and is more amenable to automation, it offers an efficient and high-throughput alternative for detecting and calibrating unbalanced rearrangements, both of the telomere region, as well as other genomic locations. 相似文献
6.
Meta-analysis of the association of beta2-adrenergic receptor polymorphisms with asthma phenotypes 总被引:8,自引:0,他引:8
Contopoulos-Ioannidis DG Manoli EN Ioannidis JP 《The Journal of allergy and clinical immunology》2005,115(5):963-972
BACKGROUND: Two common polymorphisms of the beta2-adrenergic receptor gene (Arg16Gly and Gln27Glu ) have been extensively studied for their possible association with asthma-related phenotypes, but the results of individual studies have been inconclusive. OBJECTIVE: We aimed to integrate quantitatively the available evidence on the association of the Arg16Gly and the Gln27Glu polymorphisms with asthma, nocturnal asthma, asthma severity, and bronchial hyperresponsiveness. METHODS: Meta-analysis of case-control and cohort studies using random effects models. RESULTS: A total of 28 studies were included in the meta-analysis. The summary estimates suggested that neither the Gly16 nor the Glu27 allele contributes to asthma susceptibility overall (odds ratio [OR], 1.01; 95% CI, 0.90-1.13; and OR, 0.95; 95% CI, 0.83-1.09, respectively) or to bronchial hyperresponsiveness (OR, 0.90; 95% CI, 0.77-1.05; and OR, 1.07; 95% CI, 0.94-1.22, respectively). There was a strong association of Gly16 with nocturnal asthma (OR, 2.20; 95% CI, 1.56-3.11) and a less strong association with severe or moderate rather than milder asthma (OR, 1.42; 95% CI, 1.04-1.94). No such effects were seen for the Glu27 allele (OR, 1.02; 95% CI, 0.74-1.40; and OR, 0.82; 95% CI, 0.59-1.14, respectively). Moreover, there was evidence that Gly16 homozygotes had a much higher risk for nocturnal asthma (OR, 5.15; 95% CI, 2.44-10.84) and asthma severity (OR, 2.84; 95% CI, 1.62-4.96) than the Arg16 homozygotes. CONCLUSION: The Gly16 allele of the beta2-adrenergic receptor gene predisposes to nocturnal asthma, and this may also explain the association with asthma severity. Neither polymorphism modulates the risk for bronchial hyperresponsiveness or mild asthma. 相似文献
7.
C. Loupa N. Mavroidi I. Boutsikakis O. Paniara O. Deligarou H. Manoli G. Saroglou 《Clinical microbiology and infection》2004,10(6):556-561
The epidemiology, and clinical and microbiological spectrum, of infective endocarditis (IE) in Greece was analysed in a prospective 4-year study in a tertiary hospital and a heart surgery centre in Athens. In total, 101 cases of IE (71 men, 30 women, aged 54.4 +/- 17.1 years) were studied, with a follow-up period of 3 months. Seventy-seven cases were definite and 24 possible; 59 involved native valves (native valve endocarditis; NVE), 31 prosthetic valves (prosthetic valve endocarditis; PVE), of which nine were early and 22 late, and 11 permanent pacemakers (pacemaker endocarditis; PME). There was a predominant involvement of aortic (48/101) and mitral (40/101) valves. Seven patients had rheumatic valvular disease, two had mitral valve prolapse, and eight had a previous history of IE. Thirteen and six patients had undergone dental and endoscopic procedures, respectively. In 13 patients, intravenous catheters were used within the 3 months before diagnosis of IE. There were three intravenous drug users among the patients. Staphylococcus aureus was the most important pathogen, isolated in 22% of cases, followed by viridans streptococci (19%) and coagulase-negative staphylococci (16%). Enterococcus spp. were responsible for 3%, HACEK group for 2%, and fungi for 6% of cases. Viridans streptococci were the leading cause of NVE (29%), Staphylococcus epidermidis of PVE (16%), and S. aureus of PME (54.5%). Six of 22 S. aureus and ten of 16 S. epidermidis isolates were methicillin-resistant. Surgical intervention, including total pacemaker removal, was performed in 51.5% of patients. Overall mortality was 16%, but was 29% with PVE, and was significantly higher with medical than with combined surgical and medical therapy (24.5% vs. 8%). Compared with previous studies, there were changing trends in the epidemiology, microbiology, treatment and prognosis of IE in Greece. 相似文献
8.
Pyrgaki Konstantina Argyraki Ariadne Kelepertzis Efstratios Botsou Fotini Megremi Ifigeneia Karavoltsos Sotirios Dassenakis Emmanuel Mpouras Thanasis Dermatas Dimitrios 《Bulletin of environmental contamination and toxicology》2021,106(3):446-452
Bulletin of Environmental Contamination and Toxicology - The holistic approach of Driver-Pressure-State-Impact-Response (DPSIR) methodology was applied to selected Cr(VI) impacted groundwater... 相似文献
9.
Mauro S. B. Silva Laurine Decoster Sara Trova Nour E.H. Mimouni Virginia Delli Konstantina Chachlaki Qiang Yu Ulrich Boehm Vincent Prevot Paolo Giacobini 《Proceedings of the National Academy of Sciences of the United States of America》2022,119(30)
Women with polycystic ovary syndrome (PCOS) frequently experience decreased sexual arousal, desire, and sexual satisfaction. While the hypothalamus is known to regulate sexual behavior, the specific neuronal pathways affected in patients with PCOS are not known. To dissect the underlying neural circuitry, we capitalized on a robust preclinical animal model that reliably recapitulates all cardinal PCOS features. We discovered that female mice prenatally treated with anti-Müllerian hormone (PAMH) display impaired sexual behavior and sexual partner preference over the reproductive age. Blunted female sexual behavior was associated with increased sexual rejection and independent of sex steroid hormone status. Structurally, sexual dysfunction was associated with a substantial loss of neuronal nitric oxide synthase (nNOS)-expressing neurons in the ventromedial nucleus of the hypothalamus (VMH) and other areas of hypothalamic nuclei involved in social behaviors. Using in vivo chemogenetic manipulation, we show that nNOSVMH neurons are required for the display of normal sexual behavior in female mice and that pharmacological replenishment of nitric oxide restores normal sexual performance in PAMH mice. Our data provide a framework to investigate facets of hypothalamic nNOS neuron biology with implications for sexual disturbances in PCOS.Polycystic ovary syndrome (PCOS) is a highly prevalent disease affecting 5 to 18% of women of reproductive age worldwide (1, 2). PCOS is diagnosed upon the presence of at least two out of three prime features: high circulating levels of androgens (hyperandrogenism), menstrual irregularities (oligo-anovulation), and polycystic-like ovarian morphology (2, 3). Beyond its implications leading to female infertility, the disease is associated with several metabolic disruptions, cardiovascular diseases, and psychosocial disorders (4). Among these neurological implications, it has become clear that approximately 30% or more of patients with PCOS experience sexual dysfunctions, with clinical studies reporting a high risk of low sexual arousal, desire, and satisfaction and impaired lubrication and orgasm (5–9). These symptoms allude to disturbances in brain circuits controlling sexual function in the context of PCOS.Neural circuits driving female sexual behaviors are conserved among vertebrate species operating under the influence of sex steroid hormone modulation, which is paramount for partner interaction, receptivity, and sexual performance (10, 11). Indeed, gonadal sex hormones are implicated in shaping circuit architecture in the hypothalamus during development and activating these neonatally programmed circuits over reproductive adult life in many species (12–16). The hypothalamus integrates sensorial stimuli and autonomic arousal from endogenous sex drive cues (e.g., estrous phase, energy status, hormone milieu, genital stimulation) to convey this information to other brain areas and peripheral nerves (10, 17). The ventromedial nucleus of the hypothalamus (VMH) is considered the hub of specialized neurons, with intrinsic properties driving different components of sexual behavior (18–21). The VMH harbors neurons expressing neuronal nitric oxide synthase (nNOS), the enzyme responsible for the production of nitric oxide (NO), a key gaseous neurotransmitter that stimulates female sexual behavior (22, 23) and communicates with other circuits within the social brain (24, 25). Despite current advances unraveling novel pathways in the female sexual brain with specific behavioral responses, there is a clear lack of knowledge on how disturbances in these circuits may participate in sexual dysfunctions affecting one-third of women with PCOS.Growing evidence indicates that androgen excess in utero induces a developmental reprogramming of the female fetal brain toward the manifestation of PCOS traits later in life (26–29). Some studies have suggested that the clinical signs of hyperandrogenism have detrimental sexual effects (5), indicating a negative correlation between androgen levels and sexual function in PCOS. In recent years, it has been proposed that prenatal anti-Müllerian hormone excess may trigger gestational hyperandrogenism via the inhibition of placental aromatase (29, 30) and that women with PCOS display higher circulating levels of androgens and AMH during pregnancy as compared to healthy women (29, 31). Prenatal AMH-treated mice (PAMH) reliably recapitulate all the mouse equivalents of the PCOS Rotterdam criteria (29, 32) and are thus a preclinical model to mimic the human PCOS condition. PAMH female mice also display pronounced neuroendocrine dysfunction leading to exacerbated luteinizing hormone (LH) secretion (29), as in women with PCOS (33), denoting the presence of prenatally reprogrammed defects within the gonadotropin-releasing hormone (GnRH) neuronal network. Thus, prenatal AMH excess–mediated disruptions in the female brain may be key to understanding the pathophysiology of PCOS.Here, we investigated whether prenatal AMH excess could underpin defects in sex circuits promoting sexual dysfunction in PCOS-like female mice. We uncovered a profound decrease of nNOS and progesterone receptor (PR) expression in the VMH. These anatomical changes were also associated with significant impairment of sexual receptivity in PCOS-like female mice. Nevertheless, normal sexual function in PAMH female mice was restored to control levels upon peripheral injection of NO donor. Performing a series of acute functional manipulations in freely moving female mice, we showed that chemogenetic silencing of nNOSVMH neurons in control female mice recapitulates PCOS-like sexual dysfunctions. Taken together, we unveiled a brain pathway potentially underpinning the etiology of low sexual drive in PCOS while pointing to prospective therapeutic approaches to rescue normal sexual function in these women. 相似文献
10.
Konstantina Yannakopoulou 《Journal of drug delivery science and technology.》2012,22(3):211-214