首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   3398篇
  免费   191篇
  国内免费   10篇
耳鼻咽喉   73篇
儿科学   59篇
妇产科学   66篇
基础医学   533篇
口腔科学   62篇
临床医学   198篇
内科学   633篇
皮肤病学   430篇
神经病学   283篇
特种医学   54篇
外科学   371篇
综合类   11篇
预防医学   307篇
眼科学   84篇
药学   197篇
中国医学   3篇
肿瘤学   235篇
  2023年   14篇
  2022年   20篇
  2021年   42篇
  2020年   32篇
  2019年   69篇
  2018年   83篇
  2017年   67篇
  2016年   81篇
  2015年   68篇
  2014年   96篇
  2013年   137篇
  2012年   233篇
  2011年   231篇
  2010年   154篇
  2009年   118篇
  2008年   233篇
  2007年   241篇
  2006年   216篇
  2005年   194篇
  2004年   192篇
  2003年   179篇
  2002年   210篇
  2001年   68篇
  2000年   77篇
  1999年   67篇
  1998年   38篇
  1997年   14篇
  1996年   34篇
  1995年   17篇
  1994年   17篇
  1993年   23篇
  1992年   30篇
  1991年   32篇
  1990年   28篇
  1989年   24篇
  1988年   22篇
  1987年   13篇
  1986年   18篇
  1985年   16篇
  1984年   8篇
  1980年   5篇
  1979年   8篇
  1975年   5篇
  1972年   4篇
  1968年   4篇
  1962年   6篇
  1960年   4篇
  1930年   4篇
  1925年   4篇
  1922年   4篇
排序方式: 共有3599条查询结果,搜索用时 15 毫秒
81.
As part of a national surveillance program on invasive group A streptococci (GAS), isolates that caused specific manifestations of invasive GAS disease in The Netherlands were collected between 1992 and 1996. These site-specific GAS infections involved meningitis, arthritis, necrotizing fasciitis, and puerperal sepsis. An evaluation was performed to determine whether GAS virulence factors correlate with these different disease manifestations. PCRs were developed to detect 9 genes encoding exotoxins and 12 genes encoding fibronectin binding proteins. The genetic backgrounds of all isolates were determined by M genotyping and pulsed-field gel electrophoresis (PFGE) analysis. The predominant M types included M1, M2, M3, M4, M6, M9, M12, and M28. Most M types were associated with all manifestations of GAS disease. However, M2 was found exclusively in patients with puerperal sepsis, M6 predominated in patients with meningitis, and M12 predominated in patients with GAS arthritis. While characteristic gene profiles were detected in most M types, the resolution of detection of different gene profiles within M genotypes was enhanced by PFGE analysis, which clearly demonstrated the existence of some clonal lineages among invasive GAS isolates in The Netherlands. M1 isolates comprised a single clone carrying highly mitogenic toxin genes (speA, smeZ) and were associated with toxic shock-like syndrome. Toxin profiles were highly conserved among the most virulent strains, such as M1 and M3.  相似文献   
82.
Differences in the global methylation pattern, ie hyper‐ as well as hypo‐methylation, are observed in cancers including germ cell tumours (GCTs). Related to their precursor cells, GCT methylation status differs according to histology. We investigated the methylation pattern of normal fetal, infantile, and adult germ cells (n = 103) and GCTs (n = 251) by immunohistochemical staining for 5‐ cytidine. The global methylation pattern of male germ cells changes from hypomethylation to hypermethylation, whereas female germ cells remain unmethylated at all stages. Undifferentiated GCTs (seminomas, intratubular germ cell neoplasia unclassified, and gonadoblastomas) are hypomethylated, whereas more differentiated GCTs (teratomas, yolk sac tumours, and choriocarcinomas) show a higher degree of methylation. Embryonal carcinomas show an intermediate pattern. Resistance to cisplatin was assessed in the seminomatous cell line TCam‐2 before and after demethylation using 5‐azacytidine. Exposure to 5‐azacytidine resulted in decreased resistance to cisplatin. Furthermore, after demethylation, the stem cell markers NANOG and POU5F1 (OCT3/4), as well as the germ cell‐specific marker VASA, showed increased expression. Following treatment with 5‐azacytidine, TCam‐2 cells were analysed using a high‐throughput methylation screen for changes in the methylation sites of 14 000 genes. Among the genes revealing changes, interesting targets were identified: ie demethylation of KLF11, a putative tumour suppressor gene, and hypermethylation of CFLAR, a gene previously described in treatment resistance in GCTs. Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.  相似文献   
83.
The effects of activating dopaminergic D(2/3) and D(4) receptors during activation of the subthalamic projection to the globus pallidus (GP) were explored in rat brain slices using the whole cell patch-clamp technique. Byocitin labeling and both orthodromic and antidromic activation demonstrated the integrity of some subthalamopallidal connections in in vitro parasagittal brain slices. Excitatory postsynaptic currents (EPSCs) that could be blocked by CNQX and AP5 were evoked onto pallidal neurons by local field stimulation of the subthalamopallidal pathway in the presence of bicuculline. Bath application of dopamine and quinpirole, a dopaminergic D(2)-class receptor agonist, reduced evoked EPSCs by about 35%. This effect was only partially blocked by sulpiride, a D(2/3) receptor antagonist. The sulpiride-sensitive reduction of the subthalamopallidal EPSC was associated with an increase in the paired-pulse ratio (PPR) and a reduction in the frequency but not the mean amplitude of spontaneous EPSCs (sEPSCs), indicative of a presynaptic site of action, which was confirmed by variance-mean analysis. The sulpiride-resistant EPSC reduction was mimicked by PD 168,077 and blocked by L-745,870, selective D(4) receptor agonist and antagonist, respectively, suggesting the involvement of D(4) receptors. The reduction of EPSCs produced by PD 168,077 was not accompanied by changes in PPR or the frequency of sEPSCs; however, it was accompanied by a reduction in mean sEPSC amplitude, indicative of a postsynaptic site of action. These results show that dopamine modulates subthalamopallidal excitation by presynaptic D(2/3) and postsynaptic D(4) receptors. The importance of this modulation is discussed.  相似文献   
84.

Objective

Improving adherence is a challenge and multiple barriers are likely to explain non-adherence. These barriers differ per patient and over course of the regimen. Hence, personalized interventions tailored to the specific barriers are needed. In a theoretical and evidence-based Tailored Multimedia Intervention, technology (online preparatory assessment, text messaging) was used as an add-on to a tailored counseling session (learned during a communication skills training), with the expectation of synergistic effects.

Methods

A cluster randomized controlled trial was conducted in six hospitals, eight nurses and 160 chronic patients. Patient satisfaction with communication, beliefs about medication, self-efficacy and medication adherence were assessed at initiation of the treatment and after six months.

Results

Intervention effects were found for patient satisfaction with nurses’ affective communication and self-efficacy at the initiation of treatment. The effect on self-efficacy remained after six months.

Conclusion

By combining tailored counseling with technology, this intervention resulted in positive changes in important prerequisites of medication adherence.

Practical implications

Technology can contribute significantly to health care providers’ ability to tailor information to the patients’ needs.  相似文献   
85.
Ligase IV syndrome is a rare differential diagnosis for Nijmegen breakage syndrome owing to a shared predisposition to lympho‐reticular malignancies, significant microcephaly, and radiation hypersensitivity. Only 16 cases with mutations in LIG4 have been described to date with phenotypes varying from malignancy in developmentally normal individuals, to severe combined immunodeficiency and early mortality. Here, we report the identification of biallelic truncating LIG4 mutations in 11 patients with microcephalic primordial dwarfism presenting with restricted prenatal growth and extreme postnatal global growth failure (average OFC ?10.1 s.d., height ?5.1 s.d.). Subsequently, most patients developed thrombocytopenia and leucopenia later in childhood and many were found to have previously unrecognized immunodeficiency following molecular diagnosis. None have yet developed malignancy, though all patients tested had cellular radiosensitivity. A genotype–phenotype correlation was also noted with position of truncating mutations corresponding to disease severity. This work extends the phenotypic spectrum associated with LIG4 mutations, establishing that extreme growth retardation with microcephaly is a common presentation of bilallelic truncating mutations. Such growth failure is therefore sufficient to consider a diagnosis of LIG4 deficiency and early recognition of such cases is important as bone marrow failure, immunodeficiency, and sometimes malignancy are long term sequelae of this disorder.  相似文献   
86.

Background  

Unbearable suffering is an important issue in end-of-life decisions. However, there has been no systematic, prospective, patient-oriented research which has focused on unbearable suffering, nor is there a suitable measurement instrument. This article describes the methodological development of a quantitative instrument to measure the nature and intensity of unbearable suffering, practical aspects of its use in end-stage cancer patients in general practice, and studies content validity and psychometric properties.  相似文献   
87.
Immunosuppressive therapy in renal transplant recipients (RTRs) is associated with an increased risk for the development of (pre)malignancies involving the skin and the female lower genital tract. We assessed whether yearly cervical screening was performed and evaluated the development of skin cancer and gynaecological (pre)malignancies in RTRs. Female RTRs (n = 224), transplanted between 1991 and 1995, were analysed retrospectively. Sociodemographic patient characteristics, frequency and results of cervical smears and prevalence of cutaneous, cervical, vaginal or vulvar (pre)malignancies were investigated and compared with that in the general population. A mean of 0.2 cervical smears per patient per year was found to have been performed in RTRs, which is significantly less than the recommended screening ratio of 1.0 for female RTRs (P < 0.001). The risk for RTRs to develop malignancies of the female lower genital tract was increased: twofold to sixfold for cervical intraepithelial neoplasia, threefold for cervical carcinoma and 50‐fold for vulvar carcinoma. Cervical screening is not performed in accordance with the advised yearly intervals, and the risk for RTRs to develop vulvar and cervical (pre)malignancies is increased. More attention should be paid to the vulvar and cervical surveillance of RTRs by both medical specialists and general physicians.  相似文献   
88.
There is an increasing need for simple and reliable approaches to phenotypically assess DNA repair capacities. Therefore, a modification of the alkaline comet assay was developed to determine the ability of human lymphocyte extracts to perform the initial steps of the nucleotide excision repair (NER) process, i.e. damage recognition and incision. Gel-embedded nucleoids from A549 cells, pre-exposed to 1 microM benzo[a]pyrene-diol-epoxide, were incubated with cell extracts from frozen or freshly isolated lymphocytes. The rate at which incisions are introduced and the subsequent increase in tail moment is indicative for the repair capacity of the extracts. Freshly prepared extracts from lymphocytes of human volunteers (n = 8) showed significant inter-individual variations in their DNA repair capacity, which correlated with the removal of bulky DNA lesions over a period of 48 h determined by (32)P-post-labelling (R(2) = 0.76, P = 0.005). Repeated measurements revealed a low inter-assay variation (11%). Storage of cell extracts for more than 3 weeks significantly reduced (up to 80%) the capacity to incise the damaged DNA as compared to freshly isolated extracts. This reduction was completely restored by addition of ATP to the extracts before use, as it is required for the incision step of NER. In contrast, extracts freshly prepared from frozen lymphocyte pellets can be used without loss of repair activity. DNA repair deficient XPA-/- and XPC-/- fibroblasts were used to further validate the assay. Although some residual capacity to incise the DNA was observed in these cells, the repair activity was restored to normal wild-type levels when a complementary mixture of both extracts (thereby restoring XPA and XPC deficiency) was used. These results demonstrate that this repair assay can be applied in molecular epidemiological studies to assess inter-individual differences in NER.  相似文献   
89.
It is well-known that cognitive, behavioral, and physiological reactivity to pain, such as catastrophizing, avoidance of activity, and increased physiological responses, can unfavorably affect long-term outcomes in patients with chronic pain. In line with similarities between the psychophysiology of pain and itching, corresponding mechanisms may be relevant for the maintenance of chronic itching. The goal of this study was to examine the role of self-reported cognitive, behavioral, and physiological reactivity factors on itching-related outcomes in 235 patients with chronic skin diseases suffering from chronic itching. Sequential regression analyses indicate that all 3 reactivity systems predicted itching-related outcomes. Specifically, more catastrophizing, higher levels of avoidance of activity, and heightened self-reported physiological reactivity predicted more itching, more scratching, and a reduced disease-related quality of life. The results suggest that a psychological model as described for chronic pain is a useful starting point for study of the maintaining mechanisms of chronic itching.  相似文献   
90.
AIMS: Brain abnormalities are common in preterm infants and can be reliably detected by magnetic resonance (MR) imaging at term equivalent age. The aim of the present study was to acquire population based data on brain abnormalities in extremely low gestational age (ELGA) infants from the Stockholm region and to correlate the MR findings to perinatal data, in order to identify risk factors. METHODS: All infants with gestational age <27 weeks, born in the Stockholm region between January 2004 and August 2005, were scanned on a 1.5 T MR system at term equivalent age. Images were analysed using a previously established scoring system for grey and white matter abnormalities. RESULTS: No or only mild white matter abnormalities were observed in 82% and moderate to severe white matter abnormalities in 18% of infants. The Clinical Risk Index for Babies (CRIB II) score, use of inotropes, the presence of high-grade intraventricular haemorrhages and posthaemorrhagic ventricular dilatation were associated with white matter abnormalities. CONCLUSION: The incidence of moderate to severe white matter abnormalities in a population-based cohort of ELGA infants from the Stockholm region was 18%. To examine the clinical relevance of these promising results, neurodevelopmental follow up at 30 month corrected age, is ongoing.  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号