全文获取类型
收费全文 | 349篇 |
免费 | 19篇 |
国内免费 | 1篇 |
专业分类
耳鼻咽喉 | 1篇 |
儿科学 | 9篇 |
妇产科学 | 8篇 |
基础医学 | 31篇 |
口腔科学 | 8篇 |
临床医学 | 20篇 |
内科学 | 56篇 |
神经病学 | 21篇 |
特种医学 | 7篇 |
外科学 | 72篇 |
综合类 | 3篇 |
预防医学 | 12篇 |
眼科学 | 4篇 |
药学 | 38篇 |
中国医学 | 9篇 |
肿瘤学 | 70篇 |
出版年
2023年 | 3篇 |
2022年 | 8篇 |
2021年 | 13篇 |
2020年 | 5篇 |
2019年 | 6篇 |
2018年 | 8篇 |
2017年 | 4篇 |
2016年 | 12篇 |
2015年 | 25篇 |
2014年 | 16篇 |
2013年 | 35篇 |
2012年 | 29篇 |
2011年 | 36篇 |
2010年 | 20篇 |
2009年 | 10篇 |
2008年 | 13篇 |
2007年 | 11篇 |
2006年 | 16篇 |
2005年 | 16篇 |
2004年 | 20篇 |
2003年 | 19篇 |
2002年 | 10篇 |
2001年 | 4篇 |
2000年 | 1篇 |
1999年 | 6篇 |
1997年 | 4篇 |
1995年 | 2篇 |
1994年 | 2篇 |
1993年 | 2篇 |
1992年 | 1篇 |
1988年 | 3篇 |
1985年 | 2篇 |
1984年 | 3篇 |
1983年 | 2篇 |
1979年 | 1篇 |
1976年 | 1篇 |
排序方式: 共有369条查询结果,搜索用时 15 毫秒
1.
Mucolipidoses II is a rare lysosomal storage disorder with autosomal recessive inheritance. There cases with typical clinical
features in early infancy like coarse facial features, severe psychomotor retardation and joint contractures are being reported.
All the cases had no mucopolysacchariduria. These cases had normal values of lysosomal enzymes in leucocytes but markedly
increased values in serum thus confirming mucolipidoses II. Despite the fact that there is no specific treatment, genetic
counselling and prenatal diagnosis is indicated. 相似文献
2.
Raman Iyer Shridhar Hegde Yu-E. Zhang James Dinunzio Dharmendra Singhal A. Malick Gregory Amidon 《Journal of pharmaceutical sciences》2013,102(10):3604-3613
The impact of melt extrusion (HME) and spray drying (SD) on mechanical properties of hypromellose acetate succinate (HPMCAS), copovidone, and their formulated blends was studied and compared with that of reference excipients. Tensile strength (TS), compression pressure (CP), elastic modulus (E), and dynamic hardness (Hd) were determined along with Hiestand indices using compacts prepared at a solid fraction of ~0.85. HPMCAS and copovidone exhibited lower Hd, lower CP, and lower E than the reference excipients and moderate TS. HPMCAS was found to be highly brittle based on brittle fracture index values. The CP was 24% and 61% higher for HPMCAS after SD and HME, respectively, than for unprocessed material along with a higher Hd. Furthermore, the TS of HPMCAS and copovidone decreased upon HME. Upon blending melt-extruded HPMCAS with plastic materials such as microcrystalline cellulose, the TS increased. These results suggest that SD and HME could impact reworkability by reducing deformation of materials and in case of HME, likely by increasing density due to heating and shear stress in a screw extruder. A somewhat similar effect was observed for the dynamic binding index (BId) of the excipients and formulated blends. Such data can be used to quantitate the impact of processing on mechanical properties of materials during tablet formulation development. 相似文献
3.
Ashwani Khurana Deok Jung-Beom Xiaoping He Sung-Hoon Kim Robert C. Busby Laura Lorenzon Massimo Villa Alfonso Baldi Julian Molina Matthew P. Goetz Viji Shridhar 《Clinical & experimental metastasis》2013,30(4):407-415
Sulfatase 2 (Sulf-2) has been previously shown to be upregulated in breast cancer. Sulf-2 removes sulfate moieties on heparan sulfate proteoglycans which in turn modulate heparin binding growth factor signaling. Here we report that matrix detachment resulted in decreased Sulf-2 expression in breast cancer cells and increased cleavage of poly ADP-ribose polymerase. Silencing of Sulf-2 promotes matrix detachment induced cell death in MCF10DCIS cells. In an attempt to identify Sulf-2 specific inhibitor, we found that proteasomal inhibitors such as MG132, Lactacystin and Bortezomib treatment abolished Sulf-2 expression in multiple breast cancer cell lines. Additionally, we show that Bortezomib treatment of MCF10DCIS cell xenografts in mouse mammary fat pads significantly reduced tumor size, caused massive apoptosis and more importantly reduced Sulf-2 levels in vivo. Finally, our immunohistochemistry analysis of Sulf-2 expression in cohort of patient derived breast tumors indicates that Sulf-2 is significantly upregulated in autologous metastatic lesions compared to primary tumors (p < 0.037, Pearson correlation, Chi-Square analysis). In all, our data suggest that Sulf-2 might play an important role in breast cancer progression from ductal carcinoma in situ into an invasive ductal carcinoma potentially by resisting cell death. 相似文献
4.
Jyotindu Debnath Rajesh Kumar Ankit Mathur Pawan Sharma Nikhilesh Kumar Nagaraj Shridhar Ashwani Shukla Shiv Pankaj Khanna 《The Indian journal of surgery》2015,77(2):221-226
The purposes of this study were to revisit the utility of ultrasonography (USG) as a primary imaging modality in acute appendicitis (AA) and to establish the role of CT scan as a second-line/problem-solving modality. All cases of suspected AA were referred for urgent USG. USG was done with standard protocol for appendicitis. Limited computed tomographic (CT) scan [NCCT ± CECT (IV contrast only)] was done for the lower abdomen and pelvis where sonographic findings were equivocal. One hundred and twenty-one patients were referred for USG for suspected appendicitis. Eight-four patients underwent surgery for AA based on clinical as well as imaging findings, of whom 76 had appendicitis confirmed at histopathology. Three patients were misdiagnosed (3.6 %) on USG as appendicitis. Of 76 patients of appendicitis confirmed histopathologically, 63 (82.8 %) had features of appendicitis on USG and did not require any additional imaging modality. Of 121 patients, 12 (10 %) needed CT scan because of atypical features on USG. Of these 12 patients, seven had retrocecal appendicitis, and three high-up paracolic appendicitis. USG alone had sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of 81, 88, 92.6, 71.6, and 83 %, respectively. When combined with CT scan in select cases, the sensitivity, specificity, PPV, NPV, and accuracy of combined USG + CT scan were 96 % (P?=?0.0014), 89 %, 93 %, 93.5 % (P?=?0.0001), and 93 % (P?=?0.0484), respectively. Twenty-eight (23 %) patients were given alternative diagnosis on USG. Dedicated appendiceal USG should be used as a primary imaging modality in diagnosing or excluding AA. Appendiceal CT can serve as a problem-solving modality. 相似文献
5.
Sandra Merscher-Gomez Johanna Guzman Christopher E. Pedigo Markku Lehto Robier Aguillon-Prada Armando Mendez Mariann I. Lassenius Carol Forsblom TaeHyun Yoo Rodrigo Villarreal Dony Maiguel Kevin Johnson Ronald Goldberg Viji Nair Ann Randolph Matthias Kretzler Robert G. Nelson George W. Burke III Per-Henrik Groop Alessia Fornoni the FinnDiane Study Group 《Diabetes》2013,62(11):3817-3827
Diabetic kidney disease (DKD) remains the most common cause of end-stage kidney disease despite multifactorial intervention. We demonstrated that increased cholesterol in association with downregulation of ATP-binding cassette transporter ABCA1 occurs in normal human podocytes exposed to the sera of patients with type 1 diabetes and albuminuria (DKD+) when compared with diabetic patients with normoalbuminuria (DKD−) and similar duration of diabetes and lipid profile. Glomerular downregulation of ABCA1 was confirmed in biopsies from patients with early DKD (n = 70) when compared with normal living donors (n = 32). Induction of cholesterol efflux with cyclodextrin (CD) but not inhibition of cholesterol synthesis with simvastatin prevented podocyte injury observed in vitro after exposure to patient sera. Subcutaneous administration of CD to diabetic BTBR (black and tan, brachiuric) ob/ob mice was safe and reduced albuminuria, mesangial expansion, kidney weight, and cortical cholesterol content. This was followed by an improvement of fasting insulin, blood glucose, body weight, and glucose tolerance in vivo and improved glucose-stimulated insulin release in human islets in vitro. Our data suggest that impaired reverse cholesterol transport characterizes clinical and experimental DKD and negatively influences podocyte function. Treatment with CD is safe and effective in preserving podocyte function in vitro and in vivo and may improve the metabolic control of diabetes.Diabetic kidney disease (DKD) is responsible for nearly half of the incidents of end-stage kidney disease in the U.S. (1), yet our current understanding of the pathophysiological processes responsible for DKD has led to limited improvements in patient outcomes. Multifactorial intervention reduces the rate of progression of DKD but does not prevent end-stage kidney disease in type 1 (T1D) or type 2 diabetes (T2D) (2,3). A key factor for this translation gap is the current lack of adequate mechanistic insight into DKD in humans.The kidney glomerulus is a highly specialized structure that ensures the selective ultrafiltration of plasma so that essential proteins are retained in the blood (4). Podocytes are glomerular epithelial cells that contribute to the glomerular filtration barrier through a tight regulation of actin cytoskeleton remodeling (4). Currently, the diagnosis of DKD relies on the detection of microalbuminuria (5). However, a growing body of evidence suggests that key histological lesions precede the development of albuminuria (6,7); among them, decreased podocyte number (podocytopenia) has been described as an independent predictor of DKD progression (8–12). Although we have previously shown that podocyte insulin resistance and susceptibility to apoptosis is already present at the time of onset of microalbuminuria in experimental models of DKD, the cause of podocyte injury in early DKD remains unknown (13).We used a previously established cell-based assay in which differentiated human podocytes are exposed to 4% patient sera for 24 h (14) to identify new pathways and targets in DKD. Podocytes exposed to the sera of patients with DKD showed increased cholesterol accumulation in association with downregulation of ATP-binding cassette transporter 1 (ABCA1) expression that was independent of circulating cholesterol.ABCA1 is a major regulator of cellular cholesterol homeostasis by mediating efflux to lipid-poor apolipoprotein acceptors in the bloodstream (15). ABCA1 genetic variants are strongly associated with the risk of coronary artery disease (16). Furthermore, the capacity of patient sera to induce ABCA1-mediated cholesterol efflux in macrophages is impaired in patients with T2D and incipient or overt nephropathy (17). Excessive cholesterol accumulation has been described in glomeruli of rodent models of T1D and T2D (18–20) and may contribute to DKD development and progression. Finally, inactivating mutations of ABCA1 result in Tangier disease, which causes premature atherosclerosis and proteinuria (21).Although interventions that increase ABCA1 expression (such as liver X receptor agonists) may be beneficial in DKD, they have a relatively high incidence of adverse events (22) as well as intrinsic lipogenic effects (23). We used β-cyclodextrins, cyclic oligosaccharides consisting of seven β(1-4)-glucopyranose rings, to remove cholesterol from differentiated human podocytes in vitro and from diabetic animals in vivo. The exact mechanism by which cyclodextrins (CDs) remove cholesterol from cells is not completely understood, but the formation of cholesterol/CD inclusion complexes at the membrane surface plays an important role in this process (24).We hypothesized that 2-hydroxypropyl-β-cyclodextrin, which was recently approved by the U.S. Food and Drug Administration (FDA) for the cure of Niemann-Pick disorder (25,26), would be an effective way to sequester cholesterol and to protect podocytes from cholesterol-dependent damage in DKD in vivo and in vitro. 相似文献
6.
Liza Tan Hui Jun Zhou Mikael Hartman Iyer Shridhar Ganpathi Krishnakumar Madhavan Stephen Chang 《Surgical endoscopy》2013,27(9):3308-3314
Background
To retrospectively compare the outcomes of percutaneously drained and laparoscopically drained liver abscesses.Methods
Eight-five consecutive patients with radiological evidence of liver abscess were treated at National University Hospital of Singapore from 2005 to 2011. Multivariable logistic regression was used to identify failures of intervention. This was defined as persistent objective signs of sepsis. Complications, length of antibiotic therapy, and hospital stay were recorded but not used as indicators for failure of intervention. A propensity score analysis was used to adjust for possible confounders.Results
Twenty-seven (40.3 %) patients in the percutaneous group did not respond to primary intervention compared to 2 patients (11.1 %) in the laparoscopic group (p = 0.020). Two patients within the percutaneous group died from progression of sepsis despite intervention. In the multivariate model with propensity score, laparoscopic drainage had a protective effect against failure compared to percutaneous drainage of liver abscess (odds ratio [OR], 0.03; 95 % confidence interval [CI], [0–0.4]; p = 0.008). There were no differences in complications related to the intervention (p = 0.108). Mean duration of antibiotics (p = 0.437) and hospital stay (p = 0.175) between the groups was similar.Conclusions
Laparoscopic drainage of cryptogenic liver abscesses should be considered as an option for drainage of liver abscess. 相似文献7.
Ravi Shridhar MD PhD Jessica Freilich MD Sarah E. Hoffe MD Khaldoun Almhanna MD William J. Fulp MS MPH Binglin Yue Richard C. Karl MD FACS Kenneth Meredith MD FACS 《Annals of surgical oncology》2014,21(12):3744-3750
Purpose
We sought to determine the impact of esophagectomy on survival in patients with adenocarcinoma of the esophagus cancer after chemoradiotherapy (CRT).Methods
A database of esophageal cancer was queried for nonmetastatic patients with adenocarcinoma treated between 2000 and 2011 with CRT. Overall survival (OS) and recurrence-free survival (RFS) curves were calculated according to the Kaplan–Meier method and log-rank analysis. Multivariate analysis was performed by the Cox proportional hazard model.Results
We identified 154 patients (60 without surgery; 94 with surgery) who were included in the analysis. The only differences between the 2 groups were more advanced disease stage, improved performance status, and younger age in the surgery group. Patients undergoing surgery had significantly higher survival. Median and 5-year OS for surgical patients were 4.1 years and 43.6 %, versus 1.9 years and 35.6 % for nonsurgical patients (p = 0.007). Multivariate analysis for OS and RFS revealed that factors associated with increased survival were surgical resection, tumor length < 5 cm, male gender, and lower stage. Age, tumor location, radiation dose/technique, and induction chemotherapy were not prognostic. There was a trend toward improved survival on univariate analysis (p = 0.10) and multivariate analysis (p = 0.063) for surgical patients compared to nonsurgical patients who were healthy enough for surgery before CRT (n = 38), and no difference in OS in nonsurgical patients healthy enough for surgery after CRT (n = 22).Conclusion
Esophagectomy after CRT is associated with improved survival in patients with adenocarcinoma after CRT. Trimodal therapy should continue to remain the standard of care for esophageal adenocarcinoma. 相似文献8.
Shridhar D. Baliga Abhinaba Bose Saurabh Jain 《Journal of maxillofacial and oral surgery》2014,13(2):165-175
Introduction
The administration of pre and post-operative antibiotics for open reduction and internal fixation of facial fracture is the usual norm followed. Although the benefit of antibiotic has been established in the literature, the value of post-operative administration has been questioned and yet not extensively studied or investigated. There are rising concerns over the duration and undesired effects of antibiotics. The purpose of the study was to evaluate necessity and/or efficacy of post-operative antibiotics in the open reduction of zygomatic and mandibular fracture.Methods
Sixty patients who underwent open reduction and internal fixation were divided into two groups for the trial. Ab group (30 patients) received pre, intra and post-operative antibiotics. Non-Ab group (30 patients) did not receive post-operative antibiotics though pre and intra-operative antibiotics were administered. Patients were evaluated for post-op infection at the end of 1st and 3rd week after operation.Results
Among 60 patients, 2 patients (1 from Ab group and 1 from non-Ab group) were infected; so statistically no significant difference in result was obtained (Fisher’s exact test, P value = 1).Conclusion
In this trial, the use of post-operative antibiotics in the open reduction and internal fixation of facial fracture was shown to confer no benefit/efficacy in reducing the chances of infection. 相似文献9.
Rashmi S. Patil Tejraj P. Kale S.M. Kotrashetti Shridhar D. Baliga 《Acta odontologica Scandinavica》2014,72(8):984-988
Objectives. To assess the changing mid-face fracture patterns using a computed tomography scan. Methodology: Fifty patients with mid-face trauma requiring open reduction and fixation were studied using 1.6 mm axial, sagittal, coronal and 3D images. Images were evaluated clinically, intra-operatively and finally were compared with standard Le Fort lines. Results. The male population dominated the female at a ratio of 11.5:1. The majority of the mid-face fractures were seen in the age group of 21–30 years. Road traffic accident (78%) was the major etiological factor followed by work-related accidents (12%) and assaults (10%). The CT scan analysis included categorizing the patients into three groups: (1) Fracture patterns resembling Le Fort lines (24%); (2) Fracture patterns partially resembling Le Fort lines (56%); and (3) Fracture patterns that do not resemble Le Fort lines (20%). Conclusion. With the change in the velocity of wounding object, there is a change in the mid-face fracture patterns. The majority of the cases present as a variant of classical Le Fort fractures. Computed tomography is a valuable diagnostic tool in assessing the fractures of the mid-face. 2D images are more sensitive than 3D images. However, both the images are required in delivery of an optimal treatment plan. 相似文献