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71.
Recent isolation of a novel swine-origin influenza A H3N2 variant virus [A(H3N2)v] from humans in the United States has raised concern over the pandemic potential of these viruses. Here, we analyzed the virulence, transmissibility, and receptor-binding preference of four A(H3N2)v influenza viruses isolated from humans in 2009, 2010, and 2011. High titers of infectious virus were detected in nasal turbinates and nasal wash samples of A(H3N2)v-inoculated ferrets. All four A(H3N2)v viruses possessed the capacity to spread efficiently between cohoused ferrets, and the 2010 and 2011 A(H3N2)v isolates transmitted efficiently to naïve ferrets by respiratory droplets. A dose-dependent glycan array analysis of A(H3N2)v showed a predominant binding to α2-6–sialylated glycans, similar to human-adapted influenza A viruses. We further tested the viral replication efficiency of A(H3N2)v viruses in a relevant cell line, Calu-3, derived from human bronchial epithelium. The A(H3N2)v viruses replicated in Calu-3 cells to significantly higher titers compared with five common seasonal H3N2 influenza viruses. These findings suggest that A(H3N2)v viruses have the capacity for efficient replication and transmission in mammals and underscore the need for continued public health surveillance.Seasonal epidemics and periodic pandemics are an ever-present international public health burden. During seasonal epidemics, the risk for hospitalization and death are highest among persons at either end of the age spectrum as well as for individuals with underlying medical conditions (1, 2). Although the overall impact of the 2009 influenza pandemic, caused by an H1N1 virus [A(H1N1)pdm09] was more modest than those of prior pandemics, the disproportionate disease burden among children and younger adults distinguished this pandemic from seasonal influenza (35). The A(H1N1)pdm09 virus emerged from swine, with a unique constellation of genes from human, avian, and swine influenza viruses not previously observed in nature. Swine represent a unique host because of their ability to be infected by influenza viruses from multiple species and serve as a reservoir for specific subtypes of influenza capable of infecting humans (68). Triple-reassortant swine (TRS) H1N1 viruses, which share host gene-lineage origins with A(H1N1)pdm09 viruses, have been responsible for sporadic human cases since 2005 (9, 10). The emergence of the A(H1N1)pdm09 virus, to which the majority of children and younger adults had little preexisting immunity, highlights the public health threat posed by other swine-origin influenza virus subtypes.H3N2 viruses have circulated in humans since their pandemic emergence in 1968 and are generally associated with uncomplicated disease in young healthy adults. However, epidemics caused by H3N2 viruses have been more severe than those caused by seasonal H1N1 or influenza B viruses (11, 12). In 1997–1998, human H3N2 viruses infected swine and spread widely in North American swine (68). In particular, TRS H3N2 viruses with a human lineage polymerase subunit polymerase basic 1 (PB1) gene, avian lineage PB2 and polymerase acidic (PA) genes, and swine lineage nucleoprotein (NP), matrix (M), and nonstructural (NS) genes, referred to as the triple-reassortant internal gene (TRIG) constellation, have been isolated widely in pigs throughout the United States (68, 13). From the late 1990s to 2009, these novel variants of H3N2 viruses [A(H3N2)v] were limited to transmission among swine, with only occasional detections of transmission to humans (14). However, between September and November 2010, five cases of human infection with the novel swine-origin A(H3N2)v were reported (15). Although all five recovered fully from their illness, two of the five cases were hospitalized. In 2011, 12 additional human cases were documented in the United States, with limited human-to-human transmission in some cases (1517). The 2011 A(H3N2)v viruses are similar to other A(H3N2)v viruses isolated from previous human infections over the past 2 y but are unique in that the M gene is derived from the A(H1N1)pdm09 virus. Antigenic characterization showed that the A(H3N2)v viruses are distinct from current seasonal H3N2 viruses but exhibit a low degree of serologic cross-reactivity with human H3N2 viruses that circulated in the early 1990s (6, 8, 13), suggesting that children born after this time period may be particularly susceptible to infection.The use of the ferret model has become indispensable for understanding the virulence and transmission of influenza viruses (1820), partly because ferrets and humans share similar lung physiology as well as because human and avian influenza viruses exhibit similar patterns of binding to sialic acids, the receptor for influenza viruses distributed throughout the respiratory tract in both species (21, 22). In this study, we used glycan microarrays to determine the receptor-binding preference of the A(H3N2)v viruses isolated from humans. The culture model of bronchial epithelial Calu-3 cells was used to assess viral replication, and the ferret model was used to assess pathogenicity and transmissibility. Notably, the 2010 and 2011 swine-origin H3N2 viruses replicated even more efficiently than human seasonal influenza viruses in human airway Calu-3 cells and exhibited efficient respiratory-droplet (RD) transmission in ferrets. These findings suggest that swine-origin H3N2 viruses have the potential to cause additional human disease.  相似文献   
72.
Vaginal necrosis is a late radiation tissue injury with serious morbidity complications. It is rare, and its incidence is not well assessed in prospective trials. Patient comorbidities and radiation dose can significantly increase the risk. As treatment of gynecologic malignancies often involve a multidisciplinary approach, timely diagnosis and appropriate management by physicians of the team are crucial. Untreated vaginal necrosis can lead to infection, hemorrhage, necrosis-related fistulation to the bladder or rectum, perforation, and death. In this review, we describe the pathophysiology of vaginal necrosis, its clinical course, and management options.  相似文献   
73.
BACKGROUND: Coronary artery bypass grafting (CABG) can now be performed with or without cardiopulmonary bypass. The former entails global ischemia followed by reperfusion after declamping, whereas the latter does not. In view of growing evidence that reperfusion is associated with oxidative stress, we studied the extent of oxidative stress and antioxidant status in patients undergoing on-pump and off-pump CABG to determine whether the latter significantly reduces oxidative stress. METHODS: Thirty patients were initially enrolled for the study. The inclusion criteria included patients with atherosclerotic triple vessel disease, undergoing elective CABG, with good LV function, no major risk factors for surgery, with all biochemical investigations within normal limits, having stable angina and no history of previous infarct. Patients with valvular heart disease, ventricular aneurysm, heart failure and poor left ventricular function were excluded. These were alternately posted for on-pump and off-pump CABG. Eight patients were excluded as they developed unforeseen complications during the surgery. Out of the remaining 22 patients, 13 underwent off-pump CABG and 9 underwent on-pump CABG. Five blood samples were collected; baseline, 5, 15, 60 min and 24 h after reperfusion. Samples were analyzed for thiobarbituric acid reactive substances (TBARS), glutathione (G-SH) and catalase (CAT). The results were compared with their preanaesthetic levels in both the groups and also with 20 age- and sex-matched normal healthy individuals. RESULTS: Lipid peroxidation was significantly increased after reperfusion in patients undergoing on-pump CABG, maximum increase (p<0.0001) was seen 1 h after reperfusion, whereas off-pump CABG reduces oxidative stress. The G-SH levels were significantly decreased after reperfusion in on-pump and off-pump CABG patients, maximum decrease (p<0.0001) was seen 5 min after reperfusion in on-pump CABG. The catalase activity was significantly increased after reperfusion in on-pump and off-pump CABG patients, maximum increase (p<0.0001) was seen 1 h after reperfusion in on-pump CABG. CONCLUSION: Significant increase in oxidative stress was seen in patients undergoing on-pump CABG, whereas oxidative stress was less in off-pump CABG patients. The G-SH levels were decreased and Catalase activity was increased significantly in both on-pump and off-pump CABG patients.  相似文献   
74.
75.
Objective: Our objective was to compare maternal and neonatal outcomes in patients with preterm premature rupture of membranes (PPROM) delivered prior to 34°/7 weeks upon confirmation of fetal lung maturity (FLM) to those managed expectantly until 34°/7 weeks.

Methods: We performed a retrospective cohort study of non-anomalous singleton gestations with PPROM occurring after 24 weeks delivered between 32°/7 and 34°/7 weeks from 2004 to 2012. Patients delivered upon documented FLM (+FLM) – defined as the presence of phosphatidylglycerol (PG) at 32°/7–336/7 weeks if amniotic fluid was obtainable vaginally – were compared with patients delivered without documented FLM between 32°/7 and 34°/7 weeks (expectant). Primary outcomes included maternal infection (clinically diagnosed endometritis or chorioamnionitis), placental abruption and a composite of neonatal morbidities (including but not limited to mechanical ventilation, intraventricular hemorrhage, necrotizing enterocolitis, sepsis and respiratory distress syndrome). Statistical analysis was performed using Student’s t-test for continuous variables and Chi-square or Fisher’s exact test for categorical data. Covariates were analyzed via multivariate logistic regression and adjusted odds ratios were calculated.

Results: Of 237 PPROMs delivered at 32°/7–34°/7 weeks, 74 were intentionally delivered for +FLM and 163 were expectantly managed. No cord prolapse or stillbirth was observed. Maternal infection (chorioamnionitis or endometritis) was lower in the +FLM group (aOR 0.33 95% CI 0.12–0.88). Overall, there was no difference in composite neonatal morbidity did not differ between the two groups (aOR 1.36 95% CI 0.53–3.54).

Conclusions: In patients with PPROM, delivery after confirmation of FLM at 32°/7–336/7 weeks compared with expectant management until 34°/7 weeks may prevent maternal infection without increasing neonatal morbidity.  相似文献   
76.
Objective To determine the pattern of infectious agents causing tinea capitis (TC) in adult patients in adult patients in Tunisia. Methods From January 1990 to December 2005, we retrospectively collected all cases of adult TC, confirmed by the mycological examination. Results Sixty patients (18 male, 42 female) with a mean age of 34.5 years were diagnosed as having adult TC among a total number of 1137 cases of TC (5.27%). Clinical features were polymorphic and diagnosis was made on mycological examination. Culture identified Trichophyton violaceum in 36 cases (60%), Microsporum canis in 12 cases (20%), Trichophyton schoenleini in 7 cases (12%), Trichophyton verrucosum in two cases (3.5%), and Trichophyton mentagrophytes and Trichophyton rubrum in one case (each 1.77%). Culture was negative in one case. Treatment consisted of administration of Griseofulvin at the dose of 20–25 mg/kg/d during 6–8 weeks associated with antifungal topics. A complete recovery was noted in 55 cases and relapse occurred in two patients. A scary alopecia was observed in one patient and two patients were lost to follow‐up. Conclusion Trichophyton violaceum remains the most common etiological agent of adult TC in Tunisia. Microsporum canis is rising rapidly most notably due to the high frequency of asymptomatic carriage by domestic animals.  相似文献   
77.
The present study aimed at investigating the protective effects of nerolidol (NRD) against myocardial infarction (MI) induced by isoproterenol (ISO) in Wistar rats. The rats were randomly divided into five groups, each group consisting of six rats. Group I were treated as control rats, group II received NRD (200 mg/kg b.w.) by intragastric intubation for 21 days, group III received ISO (60 mg/kg b.w) subcutaneously (s.c) for two consecutive days on 22nd and 23rd day, group IV and V received NRD (100 and 200 mg/kg b.w) as in group II and additionally ISO was given for two consecutive days (22nd and 23rd). On 24th day all the rats were sacrificed by cervical dislocation and the blood and heart samples were collected. In the present study, ISO-induced myocardial damage was indicated by the changes in body weight, heart weight and the cardiac and hepatic marker enzymes such as creatine kinase (CK), creatine kinase-MB (CK-MB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and troponin T and I (cTnT, cTnI) in the serum. In addition, the levels of lipid peroxidation products such as thiobarbituric acid reactive substances (TBARS), conjugated dines (CD), and lipid hydroperoxides (LHPs) increased significantly in the plasma and heart tissue. Activities of enzymatic antioxidants such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) in erythrocytes and heart tissue and the levels of nonenzymatic antioxidants like vitamin C, vitamin E, and reduced glutathione (GSH) in plasma and heart tissue were decreased in ISO-induced rats. Histopathological observations were also supported with the biochemical parameters. Pretreatment with NRD at different doses (100 and 200 mg/kg b.w) for 21 days prevented the above changes induced by ISO. The 200 mg/kg b.w of NRD was more pronounced than the other dose and brought back all the above parameters near to normalcy.  相似文献   
78.
Sensitive and easily applicable screening tests are greatly needed for the early detection of nervous system dysfunction in people working with neurotoxic substances. Previous studies have shown that long-term solvent exposure may cause deficits in visual perception. We, therefore, studied the effects of long-term occupational solvent exposure and chronic encephalopathy on performance in three vision tests novel in the present context. Two visual search tasks were used: the letter search test measured the speed of finding a letter in an array of numerals, and the pop-out search test required the observer to detect the presence or absence of a tilted line segment in an array of vertical line segments. With the letter contrast sensitivity test we measured the contrast threshold for the identification of band-pass filtered letters. Before testing, comprehensive eye examination was carried out to reveal any structural or functional abnormality and to ensure correct refraction. The patients had healthy eyes, 2 out of 14 had reduced contrast sensitivity (Vistech) and 5 out of 14 had deficits in colour vision (FM 100). In both visual search tasks, the patients were statistically highly significantly (p < 0.001) slower than the age-matched control observers. Instead, in the contrast sensitivity test, the difference between the patient and the control group was small relative to normal variability although still statistically significant (p < 0.05). The results suggest that visual search tests can be useful in evaluating and characterising the effects of long-term solvent exposure on visual perception. Because our patients’ letter contrast sensitivity was only moderately deteriorated, it seems that the observed defect of visual search cannot be explained by deteriorated letter identification alone, although it can be a contributory factor. Rather, the finding suggests that the speed by which visual information is transmitted and/or processed in the central visual system has become considerably slower.  相似文献   
79.
Aberrant exon 5 skipping of presenilin-2 (PS2) pre-mRNA produces a deleterious protein isoform PS2V, which is almost exclusively observed in the brains of sporadic Alzheimer's disease patients. PS2V over-expression in vivo enhances susceptibility to various endoplasmic reticulum (ER) stresses and increases production of amyloid-beta peptides. We previously purified and identified high mobility group A protein 1a (HMGA1a) as a trans-acting factor responsible for aberrant exon 5 skipping. Using heterologous pre-mRNAs, here we demonstrate that a specific HMGA1a-binding sequence in exon 5 adjacent to the 5' splice site is necessary for HMGA1a to inactivate the 5' splice site. An aberrant HMGA1a-U1 snRNP complex was detected on the HMGA1a-binding site adjacent to the 5' splice site during the early splicing reaction. A competitor 2'-O-methyl RNA (2'-O-Me RNA) consisting of the HMGA1a-binding sequence markedly repressed exon 5 skipping of PS2 pre-mRNA in vitro and in vivo. Finally, HMGA1a-induced cell death under ER stress was prevented by transfection of the competitor 2'-O-Me RNA. These results provide insights into the molecular basis for PS2V-associated neurodegenerative diseases that are initiated by specific RNA binding of HMGA1a.  相似文献   
80.

Objective

Relative dose intensity (RDI) is the ratio of delivered dose intensity of chemotherapy to standard dose intensity. In this study, we sought to determine the prognostic significance of RDI in patients with epithelial ovarian cancer (EOC).

Methods

A retrospective analysis of chemotherapy naïve patients treated between 2001 and 2008 with intravenous taxane and platinum was performed. RDI was calculated as the delivered dose intensity (total dose delivered/total time of therapy) divided by standard dose intensity calculated for each regimen and compared to progression-free survival (PFS). Multivariate recursive partitioning survival analysis was utilized.

Results

138 EOC patients completed initial taxane/platinum-based chemotherapy following surgical cytoreduction. The most common reasons for dose delays and reductions were thrombocytopenia (38%) and neutropenia (31%). 24% of treatment delays were due to social reasons such as transportation constraints or scheduling conflicts. The average RDI was 90% (range, 24-126%). The mean PFS was 31 months (range, 3-117). Patients that achieved an RDI between 70% and 110% had a mean PFS of 32 months compared to 20 months in patients with an RDI of < 70% or > 110% (p = 0.046). 14 patients (10%) had a RDI of < 70%.

Conclusions

RDI is a significant predictor of survival in patients with EOC. Effort should be made to achieve an RDI of at least 70%. Dose reductions and treatment delays could be minimized by utilizing prophylactic colony stimulating factors and educating patients about the importance of adhering to their treatment schedule.  相似文献   
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