全文获取类型
收费全文 | 1493篇 |
免费 | 80篇 |
国内免费 | 29篇 |
专业分类
耳鼻咽喉 | 9篇 |
儿科学 | 13篇 |
妇产科学 | 70篇 |
基础医学 | 199篇 |
口腔科学 | 40篇 |
临床医学 | 152篇 |
内科学 | 268篇 |
皮肤病学 | 6篇 |
神经病学 | 159篇 |
特种医学 | 23篇 |
外科学 | 139篇 |
综合类 | 67篇 |
预防医学 | 115篇 |
眼科学 | 46篇 |
药学 | 194篇 |
中国医学 | 23篇 |
肿瘤学 | 79篇 |
出版年
2023年 | 5篇 |
2022年 | 19篇 |
2021年 | 29篇 |
2020年 | 19篇 |
2019年 | 27篇 |
2018年 | 46篇 |
2017年 | 17篇 |
2016年 | 35篇 |
2015年 | 46篇 |
2014年 | 58篇 |
2013年 | 72篇 |
2012年 | 86篇 |
2011年 | 131篇 |
2010年 | 64篇 |
2009年 | 56篇 |
2008年 | 102篇 |
2007年 | 100篇 |
2006年 | 85篇 |
2005年 | 94篇 |
2004年 | 81篇 |
2003年 | 75篇 |
2002年 | 60篇 |
2001年 | 54篇 |
2000年 | 36篇 |
1999年 | 20篇 |
1998年 | 17篇 |
1997年 | 18篇 |
1996年 | 12篇 |
1995年 | 8篇 |
1994年 | 10篇 |
1993年 | 12篇 |
1992年 | 18篇 |
1991年 | 12篇 |
1990年 | 8篇 |
1989年 | 8篇 |
1988年 | 10篇 |
1987年 | 10篇 |
1986年 | 16篇 |
1985年 | 8篇 |
1984年 | 6篇 |
1983年 | 5篇 |
1982年 | 2篇 |
1981年 | 1篇 |
1977年 | 1篇 |
1973年 | 3篇 |
排序方式: 共有1602条查询结果,搜索用时 15 毫秒
121.
Zhenyuan Li Hao Yan Jiangzi Yuan Liou Cao Aiwu Lin Huili Dai Zhaohui Ni Jiaqi Qian Wei Fang 《Clinical and experimental nephrology》2018,22(2):257-265
Background
Molecular mechanisms of peritoneal dialysis (PD) ultrafiltration failure, peritoneal neo-angiogenesis, and fibrosis remain to be determined. We aimed to determine the role of heparin-binding EGF-like growth factor (HB-EGF) inhibition on angiogenesis of peritoneal membrane in a PD rat model.Methods
32 male Wistar rats were assigned into (1) control group; (2) uremic non-PD group: subtotal nephrectomy-induced uremic rats without PD; (3) uremic rats subjected to PD: uremic rats that were dialyzed with Dianeal® for 4 weeks; (4) CRM 197 group: dialyzed uremic rats were supplemented with CRM197, a specific HB-EGF inhibitor. Peritoneal transport function was examined by peritoneal equilibration test. Expression of HB-EGF and EGFR in peritoneal samples were examined by real-time PCR, immunohistochemical staining, and western blot.Results
Progressive angiogenesis and fibrosis were observed in uremic PD rats, and there were associated with decreased net ultrafiltration (nUF), increased permeability of peritoneal membrane, and reduced expression of HB-EGF and EGFR protein and mRNA in uremic PD rats compared to uremic non-PD or control groups (both p < 0.05). CRM197 significantly induced peritoneal membrane permeability, decreased nUF, increased higher vessel density, and reduced pericyte count compared to that of uremic PD rats. The levels of HB-EGF and EGFR expression negatively correlated with vessel density in peritoneal membrane (both p < 0.001).Conclusion
PD therapy was associated with peritoneal angiogenesis, functional deterioration, and downregulation of HB-EGF/EGFR. Pharmacological inhibition of HB-EGF promoted PD-induced peritoneal angiogenesis and fibrosis and ultrafiltration decline, suggesting that HB-EGF downregulation contributes to peritoneal functional deterioration in the uremic PD rat model.122.
Prevalence of carotid artery stenosis in Taiwanese patients with one ischemic stroke 总被引:5,自引:0,他引:5
PURPOSE: Ethnic differences in the distribution of atherosclerosis in the brain-supplying vessels are well described. However, only scarce data exist on the prevalence of extracranial carotid artery stenosis in Taiwanese patients who have had a single ischemic stroke. METHODS: Color-coded duplex sonography was used to evaluate the carotid arteries in a hospital-based study on 276 consecutive first-time Taiwanese stroke patients. Significant atherosclerotic lesions of the internal carotid arteries (ICA) were defined as a stenosis of more than 50% or an occlusion. RESULTS: The prevalence of significant carotid lesions was 6% (35/552) in the entire cohort and 8% (17/224) in patients with hemispheric strokes. Among patients with large-artery atheroscleroses, according to criteria of the Trial of Org 10172 in Acute Stroke Treatment, only 27% had significant extracranial ICA disease whereas 69% had intracranial vessel stenoses. Older patients tended to have more severe ICA lesions, while other risk factors were not correlated with carotid stenosis. CONCLUSION: The prevalence of more than 50% ICA stenosis was low in Taiwanese patients with first hemispheric ischemic strokes, indicating that it is not a major cause of ischemic stroke in this population. 相似文献
123.
Jawl-Shan Hwang Miaw-Jene Liou Cheng Ho Jen-Der Lin Yu-Yao Huang Chao-Jan Wang Keh-Sung Tsai Jung-Fu Chen 《Journal of bone and mineral metabolism》2010,28(3):328-333
The aim of this study was to evaluate the efficacy, safety, and tolerability of weekly alendronate administration on male
osteoporosis in Taiwan. This 6-month, randomized, open-label controlled trial enrolled 46 men with osteoporosis who were randomized
to either 70 mg alendronate once weekly (n = 23) or control (n = 23). Bone mineral density (BMD) of lumbar spine and hip and biochemical bone turnover markers were measured; adverse events
and tolerability were assessed. Subjects treated with alendronate showed a significant increase in BMD of 5.5% (vs. 2% in
control group) at the lumbar spine and 2.7% (vs. 0.7%) at the femoral neck (P < 0.05) at 6 months, respectively. There were also significant decreases in serum level of bone formation marker (bone-specific
alkaline phosphatase) and urinary excretion of bone resorption marker (deoxypyridinoline) at 3 and 6 months. Thus, alendronate
showed anti-osteoporotic effects by increasing BMD and decreasing the concentrations of bone markers. The adverse events were
mild and showed no significant difference between the two groups on safety assessments. 相似文献
124.
125.
This study elucidates the association of acrylamide metabolites, N-acetyl-S-(2-carbamoylethyl)-cysteine (AAMA), N-acetyl-S-(1-carbamoyl-2-hydroxyethyl)-cysteine (GAMA2), and N-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-cysteine (GAMA3) in urine with genetic polymorphisms of the metabolic enzymes cytochrome P450 2E1 (CYP2E1), microsomal epoxide hydrolase (mEH) in exon 3 and exon 4, glutathione transferase theta (GSTT1) and mu (GSTM1), involved in the activation and detoxification of acrylamide (AA) in humans. Eighty-five workers were recruited, including 51 AA-exposed workers and 34 administrative staffs serve as controls. Personal air sampling was performed for the exposed workers. Each subject provided pre- and post-shift urine samples and blood samples. Urinary AAMA, GAMA2 and GAMA3 levels were simultaneously quantified using liquid chromatography-electronspray ionization/tandem mass spectrometry (LC-ESI-MS/MS). CYP2E1, mEH (in exon 3 and exon 4), GSTT1, and GSTM1 were analyzed using polymerase chain reaction (PCR). Our results reveal that AA personal exposures ranged from 4.37 × 10−3 to 113.61 μg/m3 with a mean at 15.36 μg/m3. The AAMA, GAMA2, and GAMA3 levels in the exposed group significantly exceeded those in controls. The GAMAs (the sum of GAMA2 and GAMA3)/AAMA ratios, potentially reflecting the proportion of AA metabolized to glycidamide (GA), varied from 0.003 to 0.456, and indicate high inter-individual variability in the metabolism of AA to GA in this study population. Multivariate regression analysis demonstrates that GSTM1 genotypes significantly modify the excretion of urinary AAMA and the GAMAs/AAMA ratio, exon 4 of mEH was significantly associated with the urinary GAMAs levels after adjustment for AA exposures. These results suggest that mEH and/or GSTM1 may be associated with the formation of urinary AAMA and GAMAs. Further study may be needed to shed light on the role of both enzymes in AA metabolism. 相似文献
126.
Lytic cycle reactivation of Kaposi's sarcoma-associated herpesvirus (KSHV) is initiated by expression of the ORF50 gene. Here we show that YY1 protein specifically binds to the ORF50 promoter (ORF50p) region in vitro and in vivo. After treatment with chemical inducers, including sodium butyrate (SB) and TPA, the levels of YY1 protein are inversely correlated with the lytic induction of KSHV in cells. Overexpression of YY1 completely blocks the ORF50p activation in transient reporter assays, while mutation at the YY1 site in the ORF50p or knockdown of YY1 protein confers an enhancement of the ORF50p activation induced by SB and TPA. YY1 overexpression in a stable cell clone HH-B2(Dox-YY1) also inhibits expression of the ORF50 and its downstream lytic genes. On the other hand, a chimeric YY1 construct that links to its coactivator E1A can disrupt viral latency. These results imply that YY1 is involved in the regulation of KSHV reactivation. 相似文献
127.
Invasive fungal infection in systemic lupus erythematosus: an analysis of 15 cases and a literature review 总被引:2,自引:0,他引:2
OBJECTIVE: To analyse 15 cases of invasive fungal infection and mortality parameters in the largest series in the last 35 yrs of patients with systemic lupus erythematosus (SLE) at a single medical centre. METHODS: Fifteen patients with SLE and invasive fungal infections were retrospectively enrolled. Clinical and laboratory data, fungal species and infected sites, corticosteroid and immunosuppressant doses and SLE disease activity index were assessed retrospectively. Comparison and correlation analyses utilized Fisher's exact test, the chi-square test, Mann-Whitney U-test or the Wilcoxon signed-rank test where appropriate. RESULTS: In contrast to other review reports, Cryptococcus neoformans was the most commonly identified fungus in this Taiwanese series. Notably, the prevalence of autoimmune haemolytic anaemia and positive results for the anti-cardiolipin antibody in this study were significantly higher than those in SLE patients in general (P < 0.0001 and P < 0.0001, respectively). Fungal infection contributed to cause of death in 7 of 15 (46.7%) patients, of which Cryptococcus neoformans accounted for six of these infections. Low-dose prednisolone (<1 or <0.5 mg/kg/day based on arbitrary division) prior to fungal infection tended to correlate with 1 yr mortality after diagnosis of SLE (P = 0.077 or P = 0.080). However, following fungal infection, patients who died from infection itself had been prescribed with higher prednisolone dose or equivalent than surviving patients (P = 0.016). All SLE patients with fungal infections had active SLE (SLEDAI >7). CONCLUSIONS: Cryptococcus neoformans infection accounted for most fatalities in SLE patients with fungal infections in this series. Active lupus disease is probably a risk factor for fungal infection in SLE patients. Notably, low prednisolone doses prior to fungal infection or high prednisolone doses following fungal infection tended to associate with or correlated to fatality, respectively. Therefore, we suggest that different prednisolone doses prescribed at various times impact the incidence of fungal infection and its associated mortality. 相似文献
128.
Liou YJ Wang YC Chen JY Bai YM Lin CC Liao DL Chen TT Chen ML Mo GH Lai IC 《Psychiatry research》2007,153(3):271-275
Tardive dyskinesia (TD) is a neurological disorder characterized by irregular, non-rhythmic, choreoathetotic and involuntary movements in single or multiple body regions. Chronic administration of typical antipsychotic agents, which predominantly act on dopamine receptors, implicates the dopamine system in susceptibility to TD. An alternative to this dopaminergic supersensivity hypothesis in understanding the pathogenesis of TD is the glutamatergic neurotoxicity hypothesis, which implicates the N-methyl-D-aspartate (NMDA) receptor in TD pathogenesis. In the present study, the association between three polymorphisms (T-200G, C366G and C2664T) of the GRIN2B gene, which encodes the 2B subunit of the NMDA receptor, and the occurrence and severity of TD were investigated in 273 Chinese schizophrenic patients receiving long-term antipsychotic treatment (TD: 142, non-TD: 133). There was no significant association between patients' genotype and allele frequencies and TD occurrence. Among the TD patients, the differences in the total scores on the Abnormal Involuntary Movement Scale (AIMS) among the three genotypes of each polymorphism were not significant. Because the three studied markers are in weak linkage disequilibrium with each other, haplotype-based association was not carried out. We conclude that genetic variations in the human GRIN2B gene probably do not play a major role in susceptibility to, or severity of TD. 相似文献
129.
Hong CJ Liou YJ Liao DL Hou SJ Yen FC Tsai SJ 《Progress in neuro-psychopharmacology & biological psychiatry》2007,31(7):1510-1513
Aralar is a mitochondrial calcium-regulated aspartate-glutamate carrier mainly distributed in brain and skeletal muscle, and involved in the transport of aspartate from mitochondria to the cytosol of a cell. Studies have shown that the brain N-acetyl aspartate (NAA) levels are greatly decreased in aralar-deficient mice, suggesting that aralar plays an important role in the synthesis of NAA in neuronal cells. Since magnetic resonance spectroscopy studies have revealed consistently reduced NAA levels in various brain regions of schizophrenic patients and their unaffected relatives, genes that affect aralar levels or NAA metabolism in the brain may be implicated in the pathogenesis of schizophrenia. Aralar is encoded by the SLC25A12 gene. In the past this gene has been found to be associated with susceptibility to autism; in this study we tested the hypothesis that SLC25A12 genetic variants confer susceptibility to schizophrenia. Six SLC25A12 polymorphisms were studied in a sample population of 253 people with schizophrenia and 216 normal controls. Significant linkage disequilibrium was obtained among the six polymorphisms. However, neither single marker nor haplotype analysis revealed an association between variants at the SLC25A12 locus and schizophrenia, suggesting that it is unlikely that the SLC25A12 polymorphisms investigated play a substantial role in conferring susceptibility to schizophrenia in the Chinese population. Further studies with SLC25A12 variants relating to brain NAA levels in patients with schizophrenia are suggested. 相似文献
130.
Tsai SJ Liou YJ Liao DL Cheng CY Hong CJ 《Progress in neuro-psychopharmacology & biological psychiatry》2007,31(3):752-755
Disturbance in glutamate neurotransmission has been implicated in the pathophysiology of schizophrenia. Since glutamate receptor interacting protein 1 (GRIP1), a modular protein that enables anchoring of AMPA receptors via its PDZ (postsynaptic density-95/discs large/zona occludens-1) domain and modulates d-serine release, plays an important role in glutamatergic function, this study tests the hypothesis that GRIP1 genetic variants confer susceptibility to schizophrenia. This study investigated whether GRIP1 genetic polymorphisms (rs1038923 and rs4913301) cause a predisposal to schizophrenia. Two GRIP1 polymorphisms were studied in a sample population of 252 people with schizophrenia and 207 normal controls. Significant linkage disequilibrium was obtained between the two polymorphisms. Results demonstrated that neither single marker nor haplotype analysis revealed an association between variants at the GRIP1 locus and schizophrenia, suggesting that it is unlikely that the GRIP1 polymorphisms investigated play a substantial role in conferring susceptibility to schizophrenia. However, association between schizophrenia and other polymorphisms in the GRIP1 gene cannot be totally ruled out as the whole gene was not covered by the two polymorphisms studied. 相似文献