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1.
Glanzmann's thrombasthenia is a bleeding disorder, inherited in an autosomal recessive way and characterized by an absence or deficiency of the platelet glycoprotein (GP) IIb/IIIa complex. Recently, we and others demonstrated that cultured human umbilical vein endothelial cells synthesized a membrane protein complex similar to the platelet GP IIb/IIIa complex. In this article, we demonstrate that endothelial cells isolated from the umbilical vein of a newborn with Glanzmann's thrombasthenia, as compared with normal endothelial cells, show no difference in their ability to synthesize and express this GP IIb/IIIa complex. Our results indicate that Glanzmann's thrombasthenia is not accompanied by an "endotheliopathy."  相似文献   
2.
In contrast to traditional approaches to fracture risk assessment using clinical risk factors and bone mineral density (BMD), a new technique, reference point microindentation (RPI), permits direct assessment of bone quality; in vivo tibial RPI measurements appear to discriminate patients with a fragility fracture from controls. However, it is unclear how this relates to the site of the most clinically devastating fracture, the femoral neck, and whether RPI provides information complementary to that from existing assessments. Femoral neck samples were collected at surgery after low‐trauma hip fracture (n = 46; 17 male; aged 83 [interquartile range 77–87] years) and compared, using RPI (Biodent Hfc), with 16 cadaveric control samples, free from bone disease (7 male; aged 65 [IQR 61–74] years). A subset of fracture patients returned for dual‐energy X‐ray absorptiometry (DXA) assessment (Hologic Discovery) and, for the controls, a micro‐computed tomography setup (HMX, Nikon) was used to replicate DXA scans. The indentation depth was greater in femoral neck samples from osteoporotic fracture patients than controls (p < 0.001), which persisted with adjustment for age, sex, body mass index (BMI), and height (p < 0.001) but was site‐dependent, being less pronounced in the inferomedial region. RPI demonstrated good discrimination between fracture and controls using receiver‐operating characteristic (ROC) analyses (area under the curve [AUC] = 0.79 to 0.89), and a model combining RPI to clinical risk factors or BMD performed better than the individual components (AUC = 0.88 to 0.99). In conclusion, RPI at the femoral neck discriminated fracture cases from controls independent of BMD and traditional risk factors but dependent on location. The clinical RPI device may, therefore, supplement risk assessment and requires testing in prospective cohorts and comparison between the clinically accessible tibia and the femoral neck. © 2015 American Society for Bone and Mineral Research.  相似文献   
3.
Lipoproteins were measured in 618 healthy, full-term newborns. Seventy-four with a VLDL-LDL-cholesterol above 1.3 mmol/l (50 mg/dl) at birth and 25 randomly chosen controls with VLDL-LDL-cholesterol 1.3 mmol/l or below at birth were followed up at age 2. Seventy-two (52 in the high VLDL-LDL-cholesterol group and 20 in the low VLDL-LDL-cholesterol group) were followed up at age 13. At age 2 mean total cholesterol was 5.48 mmol/l (SEM 0.10) in the children with a high VLDL-LDL-cholesterol at birth, compared to 4.69 mmol/l (SEM 0.17) in the children with a low VLDL-LDL-cholesterol at birth (p less than 0.001). A difference was still present at age 13 (4.74 mmol/l; SEM 0.11 versus 4.20 mmol/l; SEM 0.14; p less than 0.01). At age 13 apolipoprotein B was 0.74 g/l (SEM 0.02) in the children with a high VLDL-LDL-cholesterol at birth, compared to 0.65 g/l (SEM 0.02) in the children with a low VLDL-LDL-cholesterol at birth (p less than 0.01). Children with high VLDL-LDL-cholesterol at birth might be more liable to high lipoprotein serum levels later in life.  相似文献   
4.
BACKGROUND & AIMS: Both recombinant human growth hormone (rhGH) and glutamine (GLN) may have beneficial anabolic actions on amino acid metabolism. The aim of this study was to evaluate the additive effects of rhGH and GLN on plasma amino acids postoperatively. METHODS: 31 females undergoing laparoscopic cholecystectomy were randomized to three groups: Group I (n=10) received 13 IU/m(2) of rhGH the morning of surgery and the following three postoperative days, together with glutamine-free TPN for the first two postoperative days. Group II (n=11) received rhGH as the first group, together with glutamine-enriched (7 g GLN/m(2)/day) TPN. Group III (n=10) received glutamine-enriched TPN as the second group, but rhGH was replaced by placebo. Daily plasma amino acid concentrations and nitrogen balance were determined. RESULTS: In the GH treated groups, the plasma concentrations of several amino acids were decreased on the third postoperative day, compared to preoperatively. This was not observed in Group III. The changes were more pronounced in Group II. In Group II the negative AV-differences of amino acids tended to be attenuated, while the patients in Group III had increased negative AV-differences. The cumulative nitrogen balance was significantly improved in the GH groups, compared with Group III. CONCLUSION: The combined treatment of growth hormone and glutamine has additive effects on AV-balances of amino acids postoperatively, whereas nitrogen balance is not further improved when adding glutamine to rhGH treatment.  相似文献   
5.
Grey seal pups (Halichoerus grypus) were collected at the time of weaning (mid-October) and fasted for 52 days at thermoneutrality in separate cages. Body weight decreased exponentially, while metabolic rate dropped 45% from an average of 2.95 +/- 0.15 (SEM) W kg-1 at day 2 of fasting to a stable level of 1.62 +/- 0.06 (SEM) W kg-1 from day 10 to day 47 of fasting. Respiratory quotient was low, indicating extensive catabolism of triglycerides, while plasma cortisol was fairly stable at 110 +/- 8 (SEM) nmol l-1 throughout the fasting period. Daily urinary output decreased from 236 +/- 20 (SEM) ml day-1 at day 2 to a stable value of 87 +/- 6 (SEM) ml day-1 between days 8 and 50 of fasting. The urine was analysed for urea, uric acid, creatinine, ammonia, total nitrogen and osmolality. Urea was always the principal excretory end-product, amounting to between 70 and 80% of the total excreted nitrogen. The urine was moderately concentrated (range 770-1300 mosmol kg-1). Total excreted urinary nitrogen decreased by 68% from 3.7 +/- 0.7 (SEM) g day-1 to 1.2 +/- 0.4 (SEM) g day-1 between days 2 and 50. The urinary nitrogen was used to calculate the daily amount of protein being oxidized and its energy content was compared with the measured basal metabolic rate of individual animals. Approximately 6% of the energy expended by grey seal pups during the post-weaning fast is derived from oxidation of protein. It is concluded that a rapid depression of basal metabolic rate and extensive blubber catabolism enable grey seal pups to endure prolonged periods of fasting without any apparent signs of discomfort or stress.  相似文献   
6.
Concentrations of plasma fibrinopeptide A (FPA) were measured by radioimmunoassay in 50 patients with venous thromboembolism or disseminated intravascular coagulation or both. A consistent discrepancy was observed in values obtained with two anti-FPA antisera. Analysis of extracts from plasma of these patients by high-performance liquid chromatography (HPLC) revealed the presence of a phosphorylated and an unphosphorylated form of the A peptide. Differences in concentrations of FPA measured with the two antisera could be accounted for by their different reactivity with phosphorylated FPA (FPA-P). The differences were abolished by treatment with alkaline phosphatase. A good correlation was observed between the FPA-P content of free A- peptide material and of fibrinogen in plasma as determined by HPLC (r = .88, P less than .001, n = 11). In patients with elevated FPA levels, the mean FPA-P content of fibrinogen was significantly higher (P less than .002, n = 13) than in patients with normal FPA levels (n = 8) and in healthy controls (n = 14). Phosphorus in fibrinogen did not correlate with fibrinogen degradation products or fibrinogen levels and became normal on adequate anticoagulation. Therefore, blood-clotting activation may lead to a high phosphate content of fibrinogen and of free FPA in plasma.  相似文献   
7.
PURPOSE: Nova Scotia has a vision screening program which assesses children aged 4[1\2] to 5[1\2] years. However, its use in younger children proved impossible. This study will examine a modified screening protocol for the younger children (3 to 4 years old) and determine its negative predictive value and minimum age for reliable application. MATERIALS AND METHODS: Public health nurses administered the study protocol to 3- to 4-year-old children. One hundred seventy-eight children were screened over two summers. Medical and family history, external inspection, as well as measures of visual acuity with the Lea Hyvarinen symbols chart and stereoacuity with Frisby plates were recorded. Results were compared with a gold standard examination that included full orthoptic and ophthalmologic evaluations. One hundred forty-one (79%) children underwent the gold standard examination. Agreement between screening and gold standard examinations was studied. RESULTS: Data showed increased concordance between screening and gold standard examination results with increasing age up to 41 months. Negative predictive value (NPV) and specificity also improved when data were separated by this age. In children <41 months old, the screening test NPV was 90%, specificity, 68%, and sensitivity, 75%. In comparison, children >/=41 months old had screening test NPV of 96%, specificity, 95%, and sensitivity, 50%. Specificity was higher in the older age group ( P < 0.001). Sensitivity was lower ( P = 0.004). CONCLUSION: This study's vision screening protocol appears better suited for children 41 months and older. They had better pass/fail reproducibility than children <41 months. The test's simplicity allows easy use by non-eye-care professionals. It could potentially lower the reliable screening age of children by 13 months, from 54 months of age (4[1\2] years old) to 41 months. This screening may miss some refractive errors and microtropia/monofixation syndrome, despite normal visual acuity, stereoacuity, and external inspection.  相似文献   
8.
This document presents the Movement Disorder Society Clinical Diagnostic Criteria for Parkinson's disease (PD). The Movement Disorder Society PD Criteria are intended for use in clinical research but also may be used to guide clinical diagnosis. The benchmark for these criteria is expert clinical diagnosis; the criteria aim to systematize the diagnostic process, to make it reproducible across centers and applicable by clinicians with less expertise in PD diagnosis. Although motor abnormalities remain central, increasing recognition has been given to nonmotor manifestations; these are incorporated into both the current criteria and particularly into separate criteria for prodromal PD. Similar to previous criteria, the Movement Disorder Society PD Criteria retain motor parkinsonism as the core feature of the disease, defined as bradykinesia plus rest tremor or rigidity. Explicit instructions for defining these cardinal features are included. After documentation of parkinsonism, determination of PD as the cause of parkinsonism relies on three categories of diagnostic features: absolute exclusion criteria (which rule out PD), red flags (which must be counterbalanced by additional supportive criteria to allow diagnosis of PD), and supportive criteria (positive features that increase confidence of the PD diagnosis). Two levels of certainty are delineated: clinically established PD (maximizing specificity at the expense of reduced sensitivity) and probable PD (which balances sensitivity and specificity). The Movement Disorder Society criteria retain elements proven valuable in previous criteria and omit aspects that are no longer justified, thereby encapsulating diagnosis according to current knowledge. As understanding of PD expands, the Movement Disorder Society criteria will need continuous revision to accommodate these advances. © 2015 International Parkinson and Movement Disorder Society  相似文献   
9.
The platelet antigens, PlA1 and PlA2, are responsible for most cases of posttransfusion purpura (PTP) and neonatal alloimmune thrombocytopenia (NAIT) in the caucasian population and are determined by two allelic forms of the platelet glycoprotein GPIIIa gene. To study the interaction between these antigens and their respective antibodies, we inserted the sequence that encodes the signal peptide and the N- terminal 66 amino acids of the PlA1 form of GPIIIa into the expression vector pGEX1. To express the PlA2 antigen, nucleotide 196 of the PlA1 coding sequence was mutated to the PlA2 allelic form. When transformed and induced in Escherichia coli, the two constructs produce glutathione S-transferase (GST)/N-terminal GPIIIa fusion proteins, one containing leucine at position 33 (PlA1), the other proline (PlA2). These proteins are easily purified in milligram quantities using glutathione-Sepharose and react specifically with their respective antibodies by immunoblot and enzyme-linked immunosorbent assay. Antigenicity of the PlA1 fusion protein in reduced glutathione increases with time; moreover, the addition of oxidized glutathione accelerates this process, presumably because of formation of the native disulfide bonds. Neutralization assays indicate that the PlA1 fusion protein competes for all of the anti-PlA1 antibody in the serum of patients with PTP and NAIT that is capable of interacting with the surface of intact platelets. This study shows that the GST/N-terminal GPIIIa fusion proteins contain conformational epitopes that mimic those involved in alloimmunization, and that regions other than the amino terminal 66 amino acids of GPIIIa are not likely to contain or be required for the development of functional PlA1 epitopes. Furthermore, these recombinant proteins can be used for the affinity-purification of clinical anti-PlA1 antibodies and specific antibody identification by western blotting, making them useful in the diagnosis of patients alloimmunized to PlA1 alloantigens.  相似文献   
10.
The increase in demand for renal replacement therapy makes it important to investigate the prognosis of the earlier stages of chronic kidney disease (CKD). We examined the change in glomerular filtration rate (GFR), and patient and renal survival in CKD stage 3 in the municipality of Troms?, a well-defined European community with a population of 58,000. All patients with estimated GFR between 30 and 59 ml/min/1.73 m(2) for more than 3 months during a 10-year study period were identified from a complete database of all 248 560 measurements of serum creatinine made in the community in the study period. Change in GFR was estimated for each patient using a multilevel model. A complete follow-up with respect to patient and renal survival was obtained from hospital databases. A total of 3047 patients was included. The median number of measurements of creatinine for each patient was 9, and the median observation time was 44 months. Mean estimated change in GFR was--1.03 ml/min/1.73 m(2)/year. Seventy-three percent of the patients experienced a decline in GFR. The 10-year cumulative incidence of renal failure was 0.04 (95% CI 0.03-0.06) and mortality 0.51 (95% CI 0.48-0.55). Female gender was associated with slower decline in GFR and better patient and renal survival. In this population-based study, the decline in GFR in CKD was slower than in previously studied selected patient groups. A high mortality pre-empted the development of renal failure in many patients. The prognosis of CKD depended strongly on gender.  相似文献   
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