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161.
162.
Natálie Klubíčková Josephine K Dermawan Elaheh Mosaieby Petr Martínek Tomáš Vaněček Veronika Hájková Nikola Ptáková Petr Grossmann Petr Šteiner Marián Švajdler Zdeněk Kinkor Květoslava Michalová Peter Szepe Lukáš Plank Stanislava Hederová Alexandra Kolenová Neofit Juriev Spasov Kemal Kosemehmetoglu Leo Pažanin Zuzana Špůrková Martin Baník Luděk Baumruk Anders Meyer Antonina Kalmykova Olena Koshyk Michal Michal Michael Michal 《The Journal of pathology》2024,263(1):61-73
Alterations in kinase genes such as NTRK1/2/3, RET, and BRAF underlie infantile fibrosarcoma (IFS), the emerging entity ‘NTRK-rearranged spindle cell neoplasms’ included in the latest WHO classification, and a growing set of tumors with overlapping clinical and pathological features. In this study, we conducted a comprehensive clinicopathological and molecular analysis of 22 cases of IFS and other kinase gene-altered spindle cell neoplasms affecting both pediatric and adult patients. Follow-up periods for 16 patients ranged in length from 10 to 130 months (mean 38 months). Six patients were treated with targeted therapy, achieving a partial or complete response in five cases. Overall, three cases recurred and one metastasized. Eight patients were free of disease, five were alive with disease, and two patients died. All cases showed previously reported morphological patterns. Based on the cellularity and level of atypia, cases were divided into three morphological grade groups. S100 protein and CD34 were at least focally positive in 12/22 and 14/22 cases, respectively. Novel PWWP2A::RET, NUMA1::RET, ITSN1::RAF1, and CAPZA2::MET fusions, which we report herein in mesenchymal tumors for the first time, were detected by RNA sequencing. Additionally, the first uterine case with BRAF and EGFR mutations and CD34 and S100 co-expression is described. DNA sequencing performed in 13 cases uncovered very rare additional genetic aberrations. The CNV profiles showed that high-grade tumors demonstrate a significantly higher percentage of copy number gains and losses across the genome compared with low- and intermediate-grade tumors. Unsupervised clustering of the tumors’ methylation profiles revealed that in 8/9 cases, the methylation profiles clustered with the IFS methylation class, irrespective of their clinicopathological or molecular features. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. 相似文献
163.
Aim
The aim of our open prospective randomized nutritional intervention study was to evaluate the effect of feeding with a standard infant formula enriched with the specific mixture of oligosaccharides on local digestive immunity system and further development of allergic and infectious diseases in young children.Material and methods
Depending on the type of feeding the infants were divided into 3 groups (with random allocation to one of the formula feeding groups): 80 infants who were breastfed, 80 infants consuming the formula supplemented with oligosaccharides, 80 infants fed with a standard formula.Results
Breastfed infants had the highest content of Bifidobacteria and Lactobacilli in feces (9.047 ± 1.075 and 7.26 ± 0.65 CFU/g accordingly). In infants fed with formula supplemented with scGOS/lcFOS fecal concentrations of Bifidobacteria and Lactobacilli were similar to those in breastfed infants (8.92 ± 1.011 and 7.22 ± 0.74 CFU/g accordingly). It was found that infants fed with breast milk and supplemented formula had significantly less allergic reactions to food products compared to the babies from the third group (3.92% and 4.84% vs. 16.98% accordingly; p < 0,05).Conclusions
The mixture of prebiotic oligosaccharides (scGOS/lcFOS – 9:1; 8 g/L) has a similar to breast milk positive impact on the factors of local digestive immunity system in formula-fed infants. This effect may reduce the risk of allergic and infectious diseases in children aged up to 18 months of life, compared with babies fed with the standard formula without oligosaccharides. 相似文献164.
Qingdu Liu Olena Davidoff Knut Niss Volker H. Haase 《The Journal of clinical investigation》2012,122(12):4635-4644
Iron demand in bone marrow increases when erythropoiesis is stimulated by hypoxia via increased erythropoietin (EPO) synthesis in kidney and liver. Hepcidin, a small polypeptide produced by hepatocytes, plays a central role in regulating iron uptake by promoting internalization and degradation of ferroportin, the only known cellular iron exporter. Hypoxia suppresses hepcidin, thereby enhancing intestinal iron uptake and release from internal stores. While HIF, a central mediator of cellular adaptation to hypoxia, directly regulates renal and hepatic EPO synthesis under hypoxia, the molecular basis of hypoxia/HIF-mediated hepcidin suppression in the liver remains unclear. Here, we used a genetic approach to disengage HIF activation from EPO synthesis and found that HIF-mediated suppression of the hepcidin gene (Hamp1) required EPO induction. EPO induction was associated with increased erythropoietic activity and elevated serum levels of growth differentiation factor 15. When erythropoiesis was inhibited pharmacologically, Hamp1 was no longer suppressed despite profound elevations in serum EPO, indicating that EPO by itself is not directly involved in Hamp1 regulation. Taken together, we provide in vivo evidence that Hamp1 suppression by the HIF pathway occurs indirectly through stimulation of EPO-induced erythropoiesis. 相似文献
165.
Su Z Lopatiuk-Tirpak O Zeidan O Sruprisan SI Meeks SL Slopsema R Flampouri S Li Z 《Physics in medicine and biology》2012,57(3):649-663
Organ motion in proton therapy affects treatment dose distribution during both double-scattering (DS) and uniform-scanning (US) deliveries. We investigated the dosimetric impact of target motion using three-dimensional polymer gel dosimeters and a programmable motion platform. A simple one-beam treatment plan with 16 cm range and 6 cm modulation was generated from the treatment planning system (TPS) in both the DS and US modes. One gel dosimeter was irradiated with a stationary DS beam. Two other gel dosimeters were irradiated with the DS and US beams while they moved in the same sinusoidal motion profile using a programmable motion platform. The dose distribution of the stationary DS delivery agreed with the TPS plan. Dosimetric comparisons between DS motion delivery and the MATLAB-based motion model showed insignificant differences. Dose-volume histograms of a cylindrical target volume inside the gel dosimeters showed target coverage degradation caused by motion. A three-dimensional gamma index calculation (3% and 3 mm) confirmed different dosimetric impacts from DS and US with the same target motion. This polymer-gel-dosimeter-based study confirmed the dosimetric impact of intrafraction target motion and its interplay with temporal delivery of different energy layers in US proton treatments. 相似文献
166.
167.
More than 45% of Australians buy health insurance for private treatment in hospital. This is despite having access to universal and free public hospital treatment. Anecdotal evidence suggests that avoidance of long waits for public treatment is one possible explanation for the high rate of insurance coverage. In this study, we investigate the effect of waiting on individual decisions to buy private health insurance. Individuals are assumed to form an expectation of their own waiting time as a function of their demographics and health status. We model waiting times using administrative data on the population hospitalised for elective procedures in public hospitals and use the parameter estimates to impute the expected waiting time and the probability of a long wait for a representative sample of the population. We find that expected waiting time does not increase the probability of buying insurance but a high probability of experiencing a long wait does. On average, waiting time has no significant impact on insurance. In addition, we find that favourable selection into private insurance, measured by self-assessed health, is no longer significant once waiting time variables are included. This result suggests that a source of favourable selection may be aversion to waiting among healthier people. 相似文献
168.
Ibis C Tuyun AF Ozsoy-Gunes Z Bahar H Stasevych MV Musyanovych RY Komarovska-Porokhnyavets O Novikov V 《European journal of medicinal chemistry》2011,46(12):5861-5867
1,4-Naphthoquinones are unique reagents in organic synthesis and have been employed in several well known and recently developed areas of application. Furthermore, these 1,4-naphthoquinones have demonstrated high reactivity in nucleophilic vinylic substitutions, in the preparation of sulfurated, (hetero)cyclic and several other transformations. This study describes the synthesis and biological evaluation of derivatives of monosulfurated naphthalene-1,4-dione (3), 3-chloro-2-ethoxy-naphthalene-1,4-dione (4), disulfurated naphthalene-1,4-dione (5), and symmetrical bis-1,4-naphthoquinones (7, 9) were obtained from the reaction of 2,3-dichloro-naphthaquinone (1) with S-, O-substituted mono-, di-, and tetrathiols, respectively. The structures of the novel products were characterized by spectroscopic methods. 相似文献
169.
170.
Anastasia Dimitropoulos Olena Zyga Sandra Russ 《Journal of autism and developmental disorders》2017,47(9):2814-2825
Here we report the feasibility and acceptability of telehealth for direct intervention in children with Prader–Willi syndrome (PWS). Children with PWS have social-cognitive challenges that are similar to children with ASD. However, developing behavioral interventions for individuals with PWS is faced with the significant challenge of enrolling enough participants for local studies where multiple visits per week are indicated for effective intervention. This study delivered a 6-week play-based intervention via telehealth directly to eight children with PWS (6–12 years). Participants completed the program with minimal behavioral or technological difficulty (#sessions M?=?11.875/12). Behavioral Intervention Rating Scale results indicate good acceptability (M?=?5.54/6.00). These findings support using telehealth in rare disorders and delivering intervention directly to children with developmental delays through this modality. 相似文献