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751.
Alves S Régulier E Nascimento-Ferreira I Hassig R Dufour N Koeppen A Carvalho AL Simões S de Lima MC Brouillet E Gould VC Déglon N de Almeida LP 《Human molecular genetics》2008,17(14):2071-2083
Machado-Joseph disease (MJD) is a fatal, dominant neurodegenerative disorder. MJD results from polyglutamine repeat expansion in the MJD-1 gene, conferring a toxic gain of function to the ataxin-3 protein. In this study, we aimed at overexpressing ataxin-3 in the rat brain using lentiviral vectors (LV), to generate an in vivo MJD genetic model and, to study the disorder in defined brain regions: substantia nigra, an area affected in MJD, cortex and striatum, regions not previously reported to be affected in MJD. LV encoding mutant or wild-type human ataxin-3 was injected in the brain of adult rats and the animals were tested for behavioral deficits and neuropathological abnormalities. Striatal pathology was confirmed in transgenic mice and human tissue. In substantia nigra, unilateral overexpression of mutant ataxin-3 led to: apomorphine-induced turning behavior; formation of ubiquitinated ataxin-3 aggregates; alpha-synuclein immunoreactivity; and loss of dopaminergic markers (TH and VMAT2). No neuropathological changes were observed upon wild-type ataxin-3 overexpression. Mutant ataxin-3 expression in striatum and cortex, resulted in accumulation of misfolded ataxin-3, and within striatum, loss of neuronal markers. Striatal pathology was confirmed by observation in MJD transgenic mice of ataxin-3 aggregates and substantial reduction of DARPP-32 immunoreactivity and, in human striata, by ataxin-3 inclusions, immunoreactive for ubiquitin and alpha-synuclein. This study demonstrates the use of LV encoding mutant ataxin-3 to produce a model of MJD and brings evidence of striatal pathology, suggesting that this region may contribute to dystonia and chorea observed in some MJD patients and may represent a target for therapies. 相似文献
752.
Alves Pedroso ML Boldt AB Pereira-Ferrari L Steffensen R Strauss E Jensenius JC Ioshii SO Messias-Reason I 《Clinical and experimental immunology》2008,152(2):258-264
Hepatitis C virus (HCV) is a major cause of hepatic disease and of liver transplantation worldwide. Mannan-binding lectin (MBL), encoded by the MBL2 gene, can have an important role as an opsonin and complement activating molecule in HCV persistence and liver injury. We assessed the MBL2 polymorphism in 102 Euro-Brazilian patients with moderate and severe chronic hepatitis C, paired for gender and age with 102 HCV seronegative healthy individuals. Six common single nucleotide polymorphisms in the MBL2 gene, three in the promoter (H/L, X/Y and P/Q) and three in exon 1 (A, the wild-type, and B, C or D also known as O) were evaluated using real-time polymerase chain reaction with fluorescent hybridization probes. The concentration of MBL in plasma was measured by enzyme-linked immunosorbent assay. The frequency of the YA/YO genotype was significantly higher in the HCV patients compared with the controls (P = 0.022). On the other hand, the genotypes associated with low levels of MBL (XA/XA, XA/YO and YO/YO) were decreased significantly in the patients with severe fibrosis (stage F4), when compared with the patients with moderate fibrosis (stage F2) (P = 0.04) and to the control group (P = 0.011). Furthermore, MBL2 genotypes containing X or O mutations were found to be associated with non-responsiveness to pginterferon and ribavirin treatment (P = 0.023). MBL2 polymorphisms may therefore be associated not only with the development of chronic hepatitis C, but also with its clinical evolution and response to treatment. 相似文献
753.
754.
A Marceline Tutu van Furth Martijn van der Kuip Anne L van Els Lydia CR Fievez Gini GC van Rijckevorsel Anton van den Ouden Marcel Jonges Matthijs RA Welkers 《Euro surveillance : bulletin européen sur les maladies transmissibles = European communicable disease bulletin》2022,27(29)
Since May 2022, an international monkeypox (MPX) outbreak has been ongoing in more than 50 countries. While most cases are men who have sex with men, transmission is not restricted to this population. In this report, we describe the case of a male child younger than 10 years with MPX in the Netherlands. Despite thorough source tracing, a likely source of infection has not been identified. No secondary cases were identified in close contacts. 相似文献
755.
Padam Raj Joshi Sagar Babu Pandey Usha Manandhar Saroj GC Gopal Sedain 《Clinical Case Reports》2022,10(4)
Astroblastoma is a rare central nervous system tumor. We reported a case of a 24‐year‐old Nepalese woman with radiological features mimicking pilocytic astrocytoma which came out to be low‐grade astroblastoma in histopathological and immunohistochemistry examination after total excision of the tumor. 相似文献
756.
Tessa Maguire RN GD FBS GD FMHN MMentHlthSc PhD Loretta Garvey RN PhD Jo Ryan RN B.Ed GC VRAM Tracy Levett-Jones RN DipHSc BN Masters Education & Work PhD Michael Olasoji RN PhD Georgina Willetts RN BN PhD 《International journal of mental health nursing》2023,32(2):544-555
Forensic mental health nurses (FMHN) provide care to address the needs of people who have mental illnesses across a range of diverse settings. The Clinical Reasoning Cycle (CRC) has been identified as a potential framework to assist FMHNs; however, adaptations were required to reflect the unique nature of the clinical setting. This study aimed to explore adaptations made to determine suitability prior to implementation in practice. Nominal Group Technique was used to explore suggested adaptations determined from a previous study and reach a consensus on the changes. Fourteen senior nurses from a state-wide Forensic mental Health (FMH) service participated. A consensus was reached for two proposed changes. Data were analysed using thematic analysis. Three main themes were interpreted from the data; FMH adaptations are warranted, the focus of the CRC, and who owns the cycle? Nurses in this study considered the need to include offence and risk issues due to the impact these factors have on the therapeutic relationship and cognitive bias; however, they also identified the need to focus on recovery-oriented care while engaging in clinical reasoning. Nurses in this study also expressed some reluctance for nursing to ‘own' the model, due to concern that ownership may cause division among the team or result in inconsistency in care. However, some participant's suggested the CRC with adaptations assisted FMH nurses to articulate their specialist skills and knowledge to others and highlight the nursing contribution to care. Further work is needed to finalize adaptations with a focus on engaging the consumer carer workforce and interdisciplinary team. 相似文献