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171.
Patients with a fracture of the proximal femur are at high risk for thromboembolic complications necessitating some form of preoperative and postoperative thromboembolic prophylaxis. Despite the knowledge that patients with a proximal femur fracture are at particularly high risk for both deep venous thrombosis and pulmonary embolism, there is no consensus on which strategy is most effective at preventing thromboembolic events in this patient population. The pathophysiology and associated risk factors for thromboembolic complications in this patient population are discussed. We present a review of studies that address the efficacy and safety of both mechanical and pharmacological methods of thromboembolic prophylaxis to assist the orthopedic surgeon in selecting among the different modalities available for thromboembolic prophylaxis.  相似文献   
172.
The diagnosis of the different forms of thalassemia is one of the important applications of analysis of globin chains. These analyses are done by high performance liquid chromatography (HPLC) using a MONO-S cation exchange column and ether is used for washing the globin powder in the final step. The presence of peroxide impurities in ether could change the structure of the globin chains. In the chromatograms, these modified globins appear as separated peaks next to the unmodified globin peaks. In these cases, the alpha/beta ratio exceed by artifact the correct value. Our study demonstrates that diagnostic centers should ensure that the ether they use is pure.  相似文献   
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BACKGROUND: Burn patients are at risk for acquiring infection because of their destroyed skin barrier and suppressed immune system, compounded by prolonged hospitalization and invasive therapeutic and diagnostic procedures. Most studies on infection in burn patients focus on burn wound infection, whereas other nosocomial infections in this patient group are not described well. OBJECTIVE: This study attempts to assess the incidence of nosocomial infection in the Ghotbeddin burn center of Shiraz. METHODS: The study was conducted prospectively during a period of 11 months from December 2000 to November 2001. All patients presenting with no signs and symptoms of infection within the first 48 hours of admission were included and examined for detecting 4 types of nosocomial infection: burn infection, urinary tract infection, pneumonia, and bloodstream infection. Centers for Disease Control and Prevention National Nosocomial Infection Surveillance system criteria were applied. RESULTS: One hundred six female patients met the inclusion criteria. Ninety-one (85.8%) acquired at least 1 infection (44.7 per 1000 patient-days), including 91 with burn infection, 28 with urinary tract infection, 56 with pneumonia, and 30 with bloodstream infection, which gives 446.7, 137.5, and 275, and 147.3 infections per 1000 patient-days, respectively. CONCLUSIONS: Considering the high incidence of nosocomial infections in our center, implementation of improved infection control practices and policies is required, and a comprehensive education campaign for all health care workers is urgently needed.  相似文献   
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Heart failure (HF) is the leading cause of morbidity and mortality in industrialized countries, creating a significant burden on both the healthcare system and quality of life. Research efforts continue to explore new pharmaceutical or surgically based approaches to HF management, but the role of nutrition as an adjunct therapy has been largely ignored. Elderly age, anorexia, malabsorption, premature satiety, and disease severity are among the factors identified as contributing to reduced nutrient intakes in patients with HF. These factors suggest that patients with HF are at increased risk of multiple-nutrient deficiencies, including B vitamins. B vitamins may be of particular therapeutic interest because of their key roles as cofactors in energy-producing pathways. Recently, impaired stores of high-energy compounds have been linked with myocardial dysfunction and prognosis in patients with HF. Therefore, deficiencies of B vitamins might contribute to reduced energy stores and disease progression. This review summarizes the existing literature both with respect to the prevalence of B vitamin deficiency as well as evidence from supplementation trials in patients with HF. The findings suggest that most of the literature in this area has focused on thiamin deficiency in patients with HF, whereas other B vitamins remain largely unstudied. Although few sporadic trials suggest a role for B vitamins in the management of HF, none are conclusive. Therefore, there is a need for larger, more robust trials to assist in defining the B vitamin requirements as well as the impact of supplementation on both morbidity and mortality in patients with HF.  相似文献   
177.
Neuronal activity is tightly coupled with brain energy metabolism. Numerous studies have suggested that lactate is equally important as an energy substrate for neurons as glucose. Lactate production is reportedly triggered by glutamate uptake, and independent of glutamate receptor activation. Here we show that climbing fibre stimulation of cerebellar Purkinje cells increased extracellular lactate by 30% within 30 s of stimulation, but not for briefer stimulation periods. To explore whether lactate production was controlled by pre- or postsynaptic events we silenced AMPA receptors with CNQX. This blocked all evoked rises in postsynaptic activity, blood flow, and glucose and oxygen consumption. CNQX also abolished rises in lactate concomitantly with marked reduction in postsynaptic currents. Rises in lactate were unaffected by inhibition of glycogen phosphorylase, suggesting that lactate production was independent of glycogen breakdown. Stimulated lactate production in cerebellum is derived directly from glucose uptake, and coupled to neuronal activity via AMPA receptor activation.  相似文献   
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Mesothelin (MSLN) is a cell-surface protein that is highly expressed by many cancers. Despite many clinical trials, there is not a Food and Drug Administration (FDA)-approved antibody-based therapy targeting MSLN. Shed MSLN is present in high concentrations in tumors and in body fluids and constitutes a major barrier to antibody-based therapies. MSLN is shed from cells by the action of proteases that cut very close to the membrane. We have identified the major protease sites in MSLN and prepared a monoclonal antibody (mAb) 15B6, that binds next to the cell membrane at the protease-sensitive region and inhibits MSLN shedding. We determined the structure of a Fab-MSLN peptide complex and found the antibody binds to residues Y-V-DLSMQEL at the C terminus of MSLN. mAb 15B6 makes very active chimeric antigen receptor (CAR) T cells whose activity is not blocked by shed MSLN. The 15B6 CAR T cells have greatly superior antitumor activity in mice than CAR T cells targeting an epitope in shed MSLN.

Mesothelin (MSLN) shedding is a barrier to the activity of antibody-based therapeutics targeting MSLN. MSLN is shed from cells by the action of proteases that cut close to the cell membrane. Monoclonal antibody (mAb) 15B6 binds to the protease-sensitive region, inhibits MSLN shedding, and makes very active chimeric antigen receptor (CAR) T cells that are greatly superior in activity in mouse tumor models to CAR T cells made with mAb SS1 that binds to a distal epitope. We ascribe this enhanced activity to binding of 15B6 CAR T cells close to the cell membrane and to avoiding the inhibitory effect of shed MSLN.MSLN is a lineage-restricted cell-surface protein that is expressed by many cancers and on normal mesothelial cells (1, 2). MSLN was discovered in a search for cell-surface proteins that were expressed in cancers but not on essential organs (3, 4) and is now known to be expressed on many human cancers (1, 2). In addition, patients with high MSLN on their tumors often have a poorer prognosis (1). The specificity and pattern of MSLN expression makes it a popular target for antibody-based therapies, including CAR T cells and bispecific T cell engagers (BiTEs) (59). Although a few major responses have been observed with antibody-based therapies targeting MSLN (1, 10, 11), there is not yet a Food and Drug Administration (FDA)-approved drug targeting MSLN.One major impediment to antibody efficacy is MSLN shedding (12). Shed MSLN inactivates antibodies and antibody-based agents such as CAR T cells and BiTEs before they reach MSLN on the tumor cells. Shedding also releases these agents from the cell surface before they have an opportunity to kill target cells. Previous studies have indicated that MSLN shedding is due to cleavage of MSLN at several different sites close to the cell membrane (12, 13). At least five different enzymes participate in the shedding process and others must exist because for some cell lines no shedding enzymes were identified (13). Another unusual aspect of shedding is that in different cancer cell lines, different enzymes are involved. Up to now ADAM10, ADAM17, BACE1, BACE2, and MMP15 have been identified (13). MSLN levels that result from tumor shedding are much higher inside tumors than in blood (14) and are very high in ascites and pleural fluid of patients with mesothelioma, where the levels can exceed 10 μg/mL. This presents a significant barrier to therapy (15).Our goal was to acquire quantitative information on the major protease sites resulting in MSLN shedding, to use this information to make a monoclonal antibody that binds to the protease site region, and to use the antibody to make CAR T cells and other targeted therapeutics. We describe here that mAb 15B6, which blocks MSLN shedding, does not react with shed MSLN and makes a very active CAR T cell that produces complete remissions of MSLN-expressing tumors in mice. We ascribe the high activity of the CAR T cells to the fact that mAb 15B6 binds to MSLN at the site where it attaches to the cell membrane and is not inactivated by shed decoy MSLN found at high concentrations inside tumors and in ascites and pleural fluid of cancer patients (14, 15). To the best of our knowledge all other antibodies to MSLN bind to shed MSLN, although the epitopes and the distance from the cell membrane vary among them (1620).  相似文献   
180.
Although there are several research articles on the detection and characterization of protein corona on the surface of various nanoparticles, there are no detailed studies on the formation, detection, and characterization of protein corona on the surface of biologically produced gold nanoparticles (AuNPs). AuNPs were prepared from Fusarium oxysporum at two different temperatures and characterized by spectrophotometry, Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), and energy-dispersive X-ray spectroscopy (EDS). The zeta potential of AuNPs was determined using a Zetasizer. AuNPs were incubated with 3 different concentrations of mouse plasma, and the hard protein corona was detected first by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and then by electrospray liquid chromatography–mass spectrometry (LC-MS). The profiles were compared to AuNPs alone that served as control. The results showed that round and oval AuNPs with sizes below 50 nm were produced at both temperatures. The AuNPs were stable after the formation of the protein corona and had sizes larger than 86 nm, and their zeta potential remained negative. We found that capping agents in the control samples contained small peptides/amino acids but almost no protein(s). After hard protein corona formation, we identified plasma proteins present on the surface of AuNPs. The identified plasma proteins may contribute to the AuNPs being shielded from phagocytizing immune cells, which makes the AuNPs a promising candidate for in vivo drug delivery. The protein corona on the surface of biologically produced AuNPs differed depending on the capping agents of the individual AuNP samples and the plasma concentration.  相似文献   
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