全文获取类型
收费全文 | 2298篇 |
免费 | 156篇 |
国内免费 | 20篇 |
专业分类
耳鼻咽喉 | 15篇 |
儿科学 | 40篇 |
妇产科学 | 16篇 |
基础医学 | 264篇 |
口腔科学 | 55篇 |
临床医学 | 205篇 |
内科学 | 581篇 |
皮肤病学 | 46篇 |
神经病学 | 259篇 |
特种医学 | 119篇 |
外科学 | 394篇 |
综合类 | 5篇 |
一般理论 | 1篇 |
预防医学 | 151篇 |
眼科学 | 20篇 |
药学 | 136篇 |
中国医学 | 10篇 |
肿瘤学 | 157篇 |
出版年
2024年 | 1篇 |
2023年 | 34篇 |
2022年 | 106篇 |
2021年 | 168篇 |
2020年 | 85篇 |
2019年 | 110篇 |
2018年 | 93篇 |
2017年 | 79篇 |
2016年 | 90篇 |
2015年 | 96篇 |
2014年 | 114篇 |
2013年 | 149篇 |
2012年 | 196篇 |
2011年 | 192篇 |
2010年 | 115篇 |
2009年 | 96篇 |
2008年 | 120篇 |
2007年 | 119篇 |
2006年 | 111篇 |
2005年 | 102篇 |
2004年 | 81篇 |
2003年 | 57篇 |
2002年 | 43篇 |
2001年 | 8篇 |
2000年 | 11篇 |
1999年 | 11篇 |
1998年 | 10篇 |
1997年 | 9篇 |
1995年 | 4篇 |
1994年 | 4篇 |
1993年 | 2篇 |
1992年 | 5篇 |
1991年 | 6篇 |
1990年 | 5篇 |
1989年 | 4篇 |
1988年 | 6篇 |
1987年 | 5篇 |
1986年 | 2篇 |
1985年 | 7篇 |
1984年 | 4篇 |
1980年 | 1篇 |
1979年 | 3篇 |
1978年 | 2篇 |
1975年 | 1篇 |
1974年 | 1篇 |
1971年 | 2篇 |
1967年 | 1篇 |
1965年 | 1篇 |
1956年 | 1篇 |
1955年 | 1篇 |
排序方式: 共有2474条查询结果,搜索用时 15 毫秒
111.
Progressive aggregation despite chaperone associations of a mutant SOD1-YFP in transgenic mice that develop ALS 下载免费PDF全文
Jiou Wang George W. Farr Caroline J. Zeiss Diego J. Rodriguez-Gil Jean H. Wilson Krystyna Furtak D. Thomas Rutkowski Randal J. Kaufman Cristian I. Ruse John R. Yates III Steve Perrin Mel B. Feany Arthur L. Horwich 《Proceedings of the National Academy of Sciences of the United States of America》2009,106(5):1392-1397
Recent studies suggest that superoxide dismutase 1 (SOD1)-linked amyotrophic lateral sclerosis results from destabilization and misfolding of mutant forms of this abundant cytosolic enzyme. Here, we have tracked the expression and fate of a misfolding-prone human SOD1, G85R, fused to YFP, in a line of transgenic G85R SOD1-YFP mice. These mice, but not wild-type human SOD1-YFP transgenics, developed lethal paralyzing motor symptoms at 9 months. In situ RNA hybridization of spinal cords revealed predominant expression in motor neurons in spinal cord gray matter in all transgenic animals. Concordantly, G85R SOD-YFP was diffusely fluorescent in motor neurons of animals at 1 and 6 months of age, but at the time of symptoms, punctate aggregates were observed in cell bodies and processes. Biochemical analyses of spinal cord soluble extracts indicated that G85R SOD-YFP behaved as a misfolded monomer at all ages. It became progressively insoluble at 6 and 9 months of age, associated with presence of soluble oligomers observable by gel filtration. Immunoaffinity capture and mass spectrometry revealed association of G85R SOD-YFP, but not WT SOD-YFP, with the cytosolic chaperone Hsc70 at all ages. In addition, 3 Hsp110's, nucleotide exchange factors for Hsp70s, were captured at 6 and 9 months. Despite such chaperone interactions, G85R SOD-YFP formed insoluble inclusions at late times, containing predominantly intermediate filament proteins. We conclude that motor neurons, initially “compensated” to maintain the misfolded protein in a soluble state, become progressively unable to do so. 相似文献
112.
Annaiah Cariappa Hiromu Takematsu Haoyuan Liu Sandra Diaz Khaleda Haider Cristian Boboila Geetika Kalloo Michelle Connole Hai Ning Shi Nissi Varki Ajit Varki Shiv Pillai 《The Journal of experimental medicine》2009,206(1):125-138
We show that the enzymatic acetylation and deacetylation of a cell surface carbohydrate controls B cell development, signaling, and immunological tolerance. Mice with a mutation in sialate:O-acetyl esterase, an enzyme that specifically removes acetyl moieties from the 9-OH position of α2–6-linked sialic acid, exhibit enhanced B cell receptor (BCR) activation, defects in peripheral B cell development, and spontaneously develop antichromatin autoantibodies and glomerular immune complex deposits. The 9-O-acetylation state of sialic acid regulates the function of CD22, a Siglec that functions in vivo as an inhibitor of BCR signaling. These results describe a novel catalytic regulator of B cell signaling and underscore the crucial role of inhibitory signaling in the maintenance of immunological tolerance in the B lineage. 相似文献
113.
Boriani G Biffi M Bacchi L Martignani C Zannoli R Butrous GS Branzi A 《European journal of clinical pharmacology》2002,58(3):165-169
OBJECTIVE: To assess the haemodynamic effects of short-term treatment with dofetilide in comparison with sotalol in patients with ischaemic heart disease. METHODS: Twelve patients with ischaemic heart disease and sustained ventricular tachycardia were treated with dofetilide [500 microg twice daily (b.i.d.)] or sotalol (160 mg b.i.d., randomised sequence separated by wash-out period) for 3-5 days. Right-heart catheterisation was performed at baseline and at the end of each short-term treatment phase. RESULTS: The main findings were a significant reduction in heart rate, mean systemic pressure and cardiac index (-13%) during treatment with sotalol. Conversely, cardiac index increased significantly during dofetilide (mean percentage change 11%) with no effect on heart rate and systemic blood pressure. CONCLUSIONS: Oral dofetilide exerts favourable haemodynamic effects in comparison with D,L-sotalol following short-term oral treatment. In view of these observations, the use of dofetilide may be proposed also in patients with ventricular tachyarrhythmias associated with impaired left-ventricular function. Whether the haemodynamic differences between dofetilide and D,L-sotalol are the basis for differences in tolerability remains to be evaluated. 相似文献
114.
Oral loading with propafenone for conversion of recent-onset atrial fibrillation: a review on in-hospital treatment 总被引:4,自引:0,他引:4
Atrial fibrillation (AF) is a very common arrhythmia. In order to treat acute AF rapidly, effective drug regimens are required. Propafenone is a class IC antiarrhythmic agent that is suitable for oral loading as it reaches peak plasma concentrations within 2 to 4 hours of administration. The use of propafenone loading in patients with AF must be based on appropriate patient selection in view of the negative inotropic effect and the potential proarrhythmic effects of the drug. A series of controlled trials in patients with recent-onset AF without heart failure who were hospitalised with enforced bed rest has shown that orally loaded propafenone (450 to 600 mg as single dose) exerts a relatively quick effect (within 3 to 4 hours) and a high rate of efficacy (72 to 78% within 8 hours). A potentially harmful effect of class IC agents is the risk of transforming AF into atrial flutter (3.5 to 5% of patients). However, atrial flutter with 1 : 1 atrioventricular response was observed in only two of 709 patients receiving propafenone (0.3% incidence). Nevertheless, the potential negative inotropic effect of propafenone demands careful patient selection, with systematic exclusion of patients with left ventricular dysfunction or congestive heart failure. Oral loading with propafenone can be considered as an episodic treatment in patients with AF recurrences, as has been proposed for other drugs in the past. However, the safety of oral loading with propafenone as an outpatient treatment in appropriately selected patients has to be assessed by appropriately designed prospective studies. 相似文献
115.
Jordan-Sciutto KL Dorsey R Chalovich EM Hammond RR Achim CL 《Journal of neuropathology and experimental neurology》2003,62(1):68-74
Cellular mechanisms implicated in Parkinson disease (PD) include oxidative stress, inflammatory response, excess dopamine, DNA damage, and loss of trophic support. These stimuli have been observed to induce changes in cell cycle proteins in several cell types. One of the key regulators of cell cycle progression is the retinoblastoma protein (pRb); therefore, we assessed the staining for pRb and its inactive hyperphosphorylated isoform, ppRb, in autopsy tissue from patients with PD. In PD we found abundant pRb staining in neuronal cytoplasm of the substantia nigra, mid-frontal cortex, and hippocampus by immunohistochemistry. In controls, pRb weakly stained nucleoli of neurons in the substantia nigra and exhibited no detectable staining in mid-frontal cortex and hippocampus. Staining for ppRb resulted in a shift from weak cytoplasmic staining in neurons from control cases to strong nuclear staining in PD cases, especially within the substantia nigra, mid-frontal cortex, and hippocampus. In the substantia nigra, ppRb also co-localized to Lewy bodies, which are a pathologic feature of PD. Lewy bodies are also found in diffuse Lewy body disease (DLBD) that do not consistently exhibit changes in pRb or ppRb. These results indicate that there are changes in pRb and its inactive phospho-isoform in neurons responding to neurodegenerative stimuli associated with PD. 相似文献
116.
117.
Painful neuropathy is a common and often distressing complication of diabetes. It has considerable impact on the social and psychological well-being of affected individuals. There are two distinct forms of painful neuropathy: an acute and self-limiting form that resolves within a year or a chronic form that can go on for years. There are now a number of drugs available for the treatment of neuropathic pain. However, some may fail to respond to these drugs or may have unacceptable adverse side effects. When this is the case, the patient's quality of life can be severely affected. Health care professionals need to assess the full impact of painful neuropathy. In this article we review a number of instruments that are used to assess the severity of painful neuropathy and its impact on the quality of life. 相似文献
118.
Gheorghe C Gheorghe L Iacob R Iacob S Simionov I Băncilă I 《Romanian journal of gastroenterology》2003,12(2):107-112
Radiation proctitis is a well-recognized complication following radiotherapy for pelvic malignancy. This study was designed to compare the efficacy and complications of argon plasma coagulation (APC) using the power setting of 50 W vs. 60 W in a group of patients with radiation proctitis. Forty-two patients were randomized to undergo APC using the electrical power setting of 60 W (23 patients, group A) or 50 W (19 patients, group B). Patients were asked to estimate the severity of major symptoms before and after APC using a scoring system graded 0-4. The score of major symptoms before and after APC, mean duration of the procedure, number of sessions, side effects/complications were noted. Statistical analysis was performed using Fisher's Exact Test and the 2-tailed p value less than 0.05 was considered statistically significant. A significant improvement of major symptoms was noted in all patients treated with APC, irrespective of the wattage we used, apart from the presence and severity of tenesmus. The mean number of treatment sessions to achieve control of bleeding was 1.34 for group A and 1.9 for group B and the mean time of treatment sessions was significantly shorter for group A (15 min vs. 17 min for group B). No significant differences in early side effects and long term complications between the two groups were evidenced. We can conclude that there is no statistical significance concerning efficacy and side effects of APC application between the 60W and 50W power setting, but the number of sessions and duration of the procedure tend to differ significantly. Rectal stenoses have been described only in patients treated with higher power settings. 相似文献
119.
Non-Hodgkin lymphomas present a wider systemic diffusion than Hodgkin lymphomas. Superficial and internal nodes, the tracheobronchial tree, and the digestive tract are almost always affected. The gastrointestinal tract is affected in 50% of the cases; the stomach is the first organ, followed by the small intestine and large intestine. The colon is affected in only approximately 0.4% of cases. The clinical picture of our patient showed abdominal pain, palpable mass, and anemia. Colonoscopy showed a tumor in the cecum (diameter, approximately 10 cm) and the biopsy indicated lymphoma. Through computed tomography, bone marrow biopsy, and measurement of beta2-microglobulin, complete staging was obtained. Right hemicolectomy was immediately performed because the large tumor could determine intestinal occlusion. Definitive diagnosis was non-Hodgkin lymphoma, type mucosa-associated lymphatic tissue B cells with a low grade of malignancy. After surgery the patient underwent six courses of chemotherapy according to the CHOP scheme (750 mg/m2 cyclophosphamide, 1.4 mg/m2 vincristine, 50 mg/m2 adriamicin, and 80 mg prednisone). Two years after surgery the patient shows no sign of the disease. 相似文献
120.