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71.
72.
Multiparametric medical imaging data can be large and are often complex. Machine learning algorithms can assist in image interpretation when reliable training data exist. In most cases, however, knowledge about ground truth (e.g. histology) and thus training data is limited, which makes application of machine learning algorithms difficult. The purpose of this study was to design and implement a learning algorithm for classification of multidimensional medical imaging data that is robust and accurate even with limited prior knowledge and that allows for generalization and application to unseen data. Local prostate cancer was chosen as a model for application and validation. 16 patients underwent combined simultaneous [11C]‐choline positron emission tomography (PET)/MRI. The following imaging parameters were acquired: T2 signal intensities, apparent diffusion coefficients, parameters Ktrans and Kep from dynamic contrast‐enhanced MRI, and PET standardized uptake values (SUVs). A spatially constrained fuzzy c‐means algorithm (sFCM) was applied to the single datasets and the resulting labeled data were used for training of a support vector machine (SVM) classifier. Accuracy and false positive and false negative rates of the proposed algorithm were determined in comparison with manual tumor delineation. For five of the 16 patients rates were also determined in comparison with the histopathological standard of reference. The combined sFCM/SVM algorithm proposed in this study revealed reliable classification results consistent with the histopathological reference standard and comparable to those of manual tumor delineation. sFCM/SVM generally performed better than unsupervised sFCM alone. We observed an improvement in accuracy with increasing number of imaging parameters used for clustering and SVM training. In particular, including PET SUVs as an additional parameter markedly improved classification results. A variety of applications are conceivable, especially for imaging of tissues without easily available histopathological correlation. Copyright © 2015 John Wiley & Sons, Ltd.  相似文献   
73.
Sphingomonas is one of the most abundant bacterial genera in the phyllosphere of wild Arabidopsis thaliana, but relative to Pseudomonas, the ecology of Sphingomonas and its interaction with plants is poorly described. We analyzed the genomic features of over 400 Sphingomonas isolates collected from local A. thaliana populations, which revealed much higher intergenomic diversity than for the considerably more uniform Pseudomonas isolates found in the same host populations. Variation in Sphingomonas plasmid complements and additional genomic features suggest high adaptability of this genus, and the widespread presence of protein secretion systems hints at frequent biotic interactions. While some of the isolates showed plant-protective phenotypes in lab tests, this was a rare trait. To begin to understand the extent of strain sharing across alternate hosts, we employed amplicon sequencing and a bulk-culturing metagenomics approach on both A. thaliana and neighboring plants. Our data reveal that both Sphingomonas and Pseudomonas thrive on other diverse plant hosts, but that Sphingomonas is a poor competitor in dying or dead leaves.

Most ecosystems, including host-associated microbiomes, are composed of a handful of common species and a wide assortment of rarer species (1, , 3). Common species are frequently implicated in direct interactions with the host. For example in the human gut, the genera Bacteroides and Prevotella, which often occupy 20% or more of the entire community (4), modulate the host immune system (5). Similarly, on and inside plant leaves, the Proteobacterial genera Sphingomonas and Pseudomonas are among the most common bacterial taxa, not only on the model plant Arabidopsis thaliana (610), but also on many other species across continents (1118).Pseudomonas–leaf interactions are widely studied (13, 1921), largely due to agricultural plant pathogens in the genus (13). Sphingomonas–leaf interactions, however, are not well understood at a genetic level or population level, despite the ubiquity of Sphingomonas on plant leaves and increasing reports of plant beneficial members of this genus (2224). Sphingomonas derives its name from its membrane-bound sphingolipids (25), structural and signaling molecules that are common in eukaryotes but found only in a few bacterial taxa (4, 26). These taxa include the previously mentioned Bacteroides and Prevotella of the gut, whose sphingolipids interact with the mammalian host and even influence host nutrition (4, 27). Sphingomonas also associate with plant roots (23, 28, 29) and seeds (22) and are common in soil and freshwater (30) among other habitats. Some strains can improve plant growth and abiotic stress tolerance in contaminated soils (31), and various others can promote plant growth through the production of growth regulators (32). Sphingomonas strains affect the abundances of other microbes (6, 22, 33, 34), and some protect against pathogenic bacteria (22, 35) or fungi (23).In our previous studies of microbes colonizing local A. thaliana in southwest (SW) Germany, we also initially focused on characterizing Pseudomonas populations, and we use those results here as a benchmark for understanding Sphingomonas ecology. We reported that Pseudomonas varied widely in bacterial load on individual plants, ranging from being nearly absent to very high titers (8, 10, 19). At the genomic level, 1,524 Pseudomonas isolates from local A. thaliana plants consisted primarily of a lineage of closely related Pseudomonas viridiflava (“OTU5” in the original publication and hereafter referred to as Pv-ATUE5) (36) that shared at least 99.9% nucleotide identity in their core genomes and the same diagnostic partial 16S rRNA gene sequence (19). Despite their similarity to each other, Pv-ATUE5 strains differed widely in pathogenicity in a gnotobiotic system, and phylogenetic analysis suggested that subgroups of Pv-ATUE5 diverged around 300,000 y ago, consistent with complex selective pressures that have not favored conquest by a single isolate (19).In this work, we sought to characterize local Sphingomonas populations at the strain level to ask if, like Pv-ATUE5, a single lineage rules the local A. thaliana bacterial community, and to determine general genetic features of plant-associated Sphingomonas. We also extended our survey onto neighboring individuals of various plant species at the site and asked to what extent Sphingomonas and Pseudomonas strains common to A. thaliana are generalists, and thus face selective pressures shaped by life on multiple host plants. This work reinforces the notion that individual Sphingomonas strains likely have broad host ranges and that they have genetic features equipping them for a multitude of biotic interactions, suggesting major roles not only in the assembly of leaf communities but also in influencing the general means by which plants sense and respond to nonpathogenic or beneficial microbes.  相似文献   
74.
The huge inter-individual differences in how people age have prompted researchers to examine whether people’s own perception of how old they are—their subjective age—could be a better predictor of relevant outcomes than their actual chronological age. Indeed, how old people feel does predict mortality hazards, and health-related measures such as walking speed may account for this association. In the present study, we extended this line of work by investigating whether subjective age also predicts walking speed and running speed in daily life or whether the predictive effects of subjective age for behavior manifest only within a controlled performance situation. We used data from 80 older participants (age range 62–82 years; M = 69.50, SD = 4.47) from the Berlin Aging Study II (BASE-II). Subjective age was assessed by self-report. Walking speed in the laboratory was measured with the Timed Up and Go test, and walking speed and running speed in real life were measured with an accelerometer. Results showed that compared to participants who felt older, those who felt younger than they actually were indeed walked faster in the laboratory, but they did not walk or run faster in real life. These patterns of results held when age, gender, education, BMI, comorbidity, depression, physical activity, and cognition were covaried. We discuss the role of stereotype threat in accounting for these results.  相似文献   
75.
Peutz-Jeghers syndrome: Diagnostic and therapeutic approach   总被引:1,自引:1,他引:1  
Peutz-Jeghers syndrome (PJS) is an inherited, autosomal dominant disorder distinguished by hamartomatous polyps in the gastrointestinal tract and pigmented mucocutaneous lesions.Prevalence of PJS is estimated from 1 in 8300 to 1 in 280 000 individuals.PJS predisposes sufferers to various malignancies (gastrointestinal, pancreatic, lung, breast, uterine, ovarian and testicular tumors).Bleeding, obstruction and intussusception are common complications in patients with PJS.Double balloon enteroscopy (DBE) allows examination and treatment of the small bowel.Polypectomy using DBE may obviate the need for repeated urgent operations and small bowel resection that leads to short bowel syndrome.Prophylaxis and polypectomy of the entire small bowel is the gold standard in PJS patients.Intraoperative enteroscopy (IOE) was the only possibility for endoscopic treatment of patients with PJS before the DBE era.Both DBE and IOE facilitate exploration and treatment of the small intestine.DBE is less invasive and more convenient for the patient.Both procedures are generally safe and useful.An overall recommendation for PJS patients includes not only gastrointestinal multiple polyp resolution, but also regular lifelong cancer screening (colonoscopy, upper endoscopy, computed tomography, magnetic resonance imaging or ultrasound of the pancreas, chest X-ray, mammography and pelvic examination with ultrasound in women, and testicular examination in men).Although the incidence of PJS is low, it is important for clinicians to recognize these disorders to prevent morbidity and mortality in these patients, and to perform presymptomatic testing in the first-degree relatives of PJS patients.  相似文献   
76.
77.
The identification of single-nucleotide polymorphisms (SNPs) in genes putatively related to pathophysiological processes in major depressive disorder (MDD) might improve both diagnosis and personalized treatment strategies eventually leading to more effective interventions. Considering the important role of the glucocorticoid receptor and the related FK506 binding protein 51 (FKBP51) in the pathophysiology of MDD, we aimed to investigate putative associations between variants of FKBP5, the coding gene of FKBP51, with antidepressant treatment resistance and MDD susceptibility.Nine common SNPs of the FKBP5 gene prioritized based on location and, putative or known functions were genotyped in Han Chinese population, including MDD patients with or without antidepressant-treatment resistance and healthy controls. Associations of FKBP5 SNPs with MDD susceptibility and treatment response were examined in the whole group of MDD patients, as well as in subgroups stratified by antidepressant treatment resistance, compared with healthy controls.In total, 181 Han Chinese patients with MDD and 80 healthy controls were recruited. No significant SNP or haplotype associations were observed in the whole patient group. There were nominal significant differences both for the haplotype block with SNPs in strong LD (r2 > 0.8, P = .040) and haplotype block with SNPs in moderate LD (r2 > 0.1, P = .017) between the haplotype distributions of patients with antidepressant treatment resistance (n = 81) and healthy controls, but both significances did not survive multiple testing correction. Furthermore, no specific haplotype could be observed causing a significant difference in any combination between all comparisons.No associations were observed of FKBP5 variants with MDD or antidepressant treatment response. The lack of associations might be due to the relatively small sample size of this study (power ranged from 0.100 to 0.752). A follow-up study will need larger, better phenotyped, and more homogeneous samples to draw a definitive conclusion regarding the involvement of this gene in MDD.  相似文献   
78.
It has been shown that iron (III) impairs the function of polymorphonuclear granulocytes (PMN). We have studied the effect of iron (II), on the membrane function of PMN, by assessing the uptake of radiolabelled Staphylococcus aureus by these cells. Iron (II), significantly impaired PMN phagocytic function. Addition of ascorbic acid reduced uptake further. Ferrous ascorbate, molar ratio 1:20, impaired phagocytic capacity of PMN significantly at iron concentrations as low as 1-10 microM. The toxic effect of iron (II) was not observed when desferrioxamine or transferrin was present in the incubation medium. The oxygen-free radical scavengers thiourea, mannitol and catalase prevented toxicity mediated by ferrous ammoniumsulphate but not by ferrous ascorbate (molar ratio of 1:20). Although high concentrations of ascorbic acid inhibited the generation of .OH and also the formation of the DMPO-.OH adduct by zymosan stimulated PMN, toxicity of iron increased. Iron (II) impaired the uptake of S. aureus by PMN of a patient with chronic granulomatous disease while iron (III) did not. Iron mediated impairment of PMN function is not only a result of the generation of toxic oxygen metabolites but also of direct interaction of iron (II) or an iron (II)-oxygen intermediate with molecules of the cell membrane.  相似文献   
79.
Fanconi anemia (FA) is a genetically heterogeneous chromosomal instability syndrome associated with multiple congenital abnormalities, aplastic anemia, and cancer. We report that a deletion mutation in the FANCG gene (c.637_643delTACCGCC) was present in 82% of FA patients in the black populations of Southern Africa. These patients originated from South Africa, Swaziland, Mozambique, and Malawi. The mutation was found on the same haplotype and was present in 1% of controls from the black South African population. These data indicate that the birth incidence of FA in this population is higher than 1 in 40 000, which is much higher than previously supposed, and suggest that the FANCG deletion is an ancient founder mutation in Bantu-speaking populations of sub-Saharan Africa. Diagnostic screening is now possible by means of a simple DNA test.  相似文献   
80.
BACKGROUND: The diagnostic management of patients with chest pain remains a clinical challenge. Magnetocardiography (MCG) is a noninvasive method for the recording of cardiac electromagnetic signals at multiple sites above the chest cage. Contrary to electrocardiogram (ECG) the magnetic field is unaltered by surrounding tissues. The present study aimed to analyze the diagnostic value of an unshielded four-channel MCG for the detection of coronary artery disease (CAD) in patients with chest pain. METHODS: The study included 417 subjects: 177 patients with angiographically documented CAD (stenoses > or =50%), 123 symptomatic patients without hemodynamically relevant stenosis (nCAD) and 117 healthy subjects. Twelve-lead ECG was obtained in all subjects. The magnetocardiography recordings were taken from 36 positions at rest. From these current density vector maps were generated during the ST-T interval. Each map was classified using a classification system with a scale from 0 (normal) to 4 (grossly abnormal). RESULTS: While the ECG was normal in all subjects the MCG revealed typical differences. In normals most maps were classified as category 0, 1 or 2, in nCAD and more so in CAD patients the categories 3 and 4 prevailed. Using a cut-off value of 39.2% for the discrimination between normals and CAD patients sensitivity was 73.3%, specificity 70.1%. CONCLUSION: Contrary to ECG, unshielded MCG reveals significant differences between normals and symptomatic patients with and without relevant stenoses using current density reconstruction during repolarization at rest. This method might be a suitable noninvasive tool for the management of patients with chest pain.  相似文献   
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