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561.
Members of the FGF family play diverse roles in patterning, cell proliferation and differentiation during embryogenesis. To begin to address their function during craniofacial development we have analyzed the expression of 18 members of the Fgf family (Fgf1-15, -17, -18 and -20) and the four members of the FGF-receptor family in the prospective midfacial region between E9.5 and E11.5 by whole-mount in situ hybridization. We show that at E9.5, Fgf3, -8, -9, -10 and -17 are broadly expressed in midfacial ectoderm. Concomitant with the outgrowth of the nasal processes at E10.5, expression of Fgf3, -8, -9, -10, -15, -17 and -18 was detected in spatially restricted regions of ectoderm at the edge of the nasal pit and at the oral edge of the medial nasal process. Expression of Fgf8, Fgf9, Fgf10 and Fgf17 was still observed in these domains at E11.5. In contrast to the restricted expression patterns of the ligands, FgfR1 and FgfR2 were broadly expressed in facial mesenchyme and ectoderm, respectively, indicating a wide competence of midfacial tissue to respond to FGF signaling. 相似文献
562.
Wiedon A Tölle M Bastine J Schuchardt M Huang T Jankowski V Jankowski J Zidek W van der Giet M 《Biochemical and biophysical research communications》2012,417(3):1035-1040
The recently discovered dinucleotide uridine adenosine tetraphosphate (Up(4)A) was found in human plasma and characterized as endothelium-derived vasoconstrictive factor (EDCF). A further study revealed a positive correlation between Up(4)A and vascular smooth muscle cell (VSMC) proliferation. Due to the dominant role of migration in the formation of atherosclerotic lesions our aim was to investigate the migration stimulating potential of Up(4)A. Indeed, we found a strong chemoattractant effect of Up(4)A on VSMC by using a modified Boyden chamber. This migration dramatically depends on osteopontin secretion (OPN) revealed by the reduction of the migration signal down to 23% during simultaneous incubation with an OPN-blocking antibody. Due to inhibitory patterns using specific and unspecific purinoreceptor inhibitors, Up(4)A mediates it's migratory signal mainly via the P2Y(2). The signaling behind the receptor was investigated with luminex technique and revealed an activation of the extracellular signal-regulated kinases 1 and 2 (ERK1/2) pathway. By use of the specific PDGF receptor (PDGFR) inhibitor AG1296 and siRNA technique against PDGFR-β we found a strongly reduced migration signal after Up(4)A stimulation in the PDGFR-β knockdown cells compared to control cells. In this study, we present substantiate data that Up(4)A exhibits migration stimulating potential probably involving the signaling cascade of MEK1 and ERK1/2 as well as the matrix protein OPN. We further suggest that the initiation of the migration process occurs predominant through direct activation of the P2Y(2) by Up(4)A and via transactivation of the PDGFR. 相似文献
563.
Kaestli M Schmid M Mayo M Rothballer M Harrington G Richardson L Hill A Hill J Tuanyok A Keim P Hartmann A Currie BJ 《Environmental microbiology》2012,14(8):2058-2070
Melioidosis is an emerging infectious disease of humans and animals in the tropics caused by the soil bacterium Burkholderia pseudomallei. Despite high fatality rates, the ecology of B.pseudomallei remains unclear. We used a combination of field and laboratory studies to investigate B.pseudomallei colonization of native and exotic grasses in northern Australia. Multivariable and spatial analyses were performed to determine significant predictors for B.pseudomallei occurrence in plants and soil collected longitudinally from field sites. In plant inoculation experiments, the impact of B.pseudomallei upon these grasses was studied and the bacterial load semi-quantified. Fluorescence in situ hybridization and confocal laser scanning microscopy were performed to localize the bacteria in plants. Burkholderia pseudomallei was found to inhabit not only the rhizosphere and roots but also aerial parts of specific grasses. This raises questions about the potential spread of B.pseudomallei by grazing animals whose droppings were found to be positive for these bacteria. In particular, B.pseudomallei readily colonized exotic grasses introduced to Australia for pasture. The ongoing spread of these introduced grasses creates new habitats suitable for B.pseudomallei survival and may be an important factor in the evolving epidemiology of melioidosis seen both in northern Australia and elsewhere globally. 相似文献
564.
Thomas F Barbeyron T Tonon T Génicot S Czjzek M Michel G 《Environmental microbiology》2012,14(9):2379-2394
565.
S Lorenzetti T Gülay M Stoop R List H Gerber F Schellenberg E Stüssi 《Journal of strength and conditioning research / National Strength & Conditioning Association》2012,26(10):2829-2836
ABSTRACT: Lorenzetti, S, Gülay, T, Stoop, M, List, R, Gerber, H, Schellenberg, F, and Stüssi, E. Comparison of the angles and corresponding moments in the knee and hip during restricted and unrestricted squats. J Strength Cond Res 26(10): 2829-2836, 2012-The aim of this study was to compare the angles and corresponding moments in the knee and hip during squats. Twenty subjects performed restricted and unrestricted squats with barbell loads that were 0, ?, and ? their body weight. The experimental setup consisted of a motion capture system and 2 force plates. The moments were calculated using inverse dynamics. During the unrestricted squats, the maximum moments in the knee were significantly higher, and those in the hip were significantly lower than during restricted squats. At the lowest position, the maximum knee flexion angles were approximately 86° for the restricted and approximately 106° for the unrestricted techniques, whereas the maximum hip flexion angle was between 95° and 100°. The higher moments in the hip during restricted squats suggest a higher load of the lower back. Athletes who aim to strengthen their quadriceps should consider unrestricted squats because of the larger knee load and smaller back load. 相似文献
566.
Bierhaus A Fleming T Stoyanov S Leffler A Babes A Neacsu C Sauer SK Eberhardt M Schnölzer M Lasitschka F Neuhuber WL Kichko TI Konrade I Elvert R Mier W Pirags V Lukic IK Morcos M Dehmer T Rabbani N Thornalley PJ Edelstein D Nau C Forbes J Humpert PM Schwaninger M Ziegler D Stern DM Cooper ME Haberkorn U Brownlee M Reeh PW Nawroth PP 《Nature medicine》2012,18(6):926-933
This study establishes a mechanism for metabolic hyperalgesia based on the glycolytic metabolite methylglyoxal. We found that concentrations of plasma methylglyoxal above 600 nM discriminate between diabetes-affected individuals with pain and those without pain. Methylglyoxal depolarizes sensory neurons and induces post-translational modifications of the voltage-gated sodium channel Na(v)1.8, which are associated with increased electrical excitability and facilitated firing of nociceptive neurons, whereas it promotes the slow inactivation of Na(v)1.7. In mice, treatment with methylglyoxal reduces nerve conduction velocity, facilitates neurosecretion of calcitonin gene-related peptide, increases cyclooxygenase-2 (COX-2) expression and evokes thermal and mechanical hyperalgesia. This hyperalgesia is reflected by increased blood flow in brain regions that are involved in pain processing. We also found similar changes in streptozotocin-induced and genetic mouse models of diabetes but not in Na(v)1.8 knockout (Scn10(-/-)) mice. Several strategies that include a methylglyoxal scavenger are effective in reducing methylglyoxal- and diabetes-induced hyperalgesia. This previously undescribed concept of metabolically driven hyperalgesia provides a new basis for the design of therapeutic interventions for painful diabetic neuropathy. 相似文献
567.
Background
Early predictors for the development of stroke-associated infection may identify patients at high risk and reduce post-stroke infection and mortality.Methods
In 383 prospectively enrolled acute stroke patients we assessed time point and type of post-stroke infections (i.e. pneumonia, urinary tract infection (UTI) other infection (OI)). Blood samples were collected on admission, and days 1, and 3 to assess white blood cells (WBC), monocytes, C-reactive protein (CRP), procalcitonin (PCT), and copeptin. To determine the magnitude of association with the development of infections, odds ratios (OR) were calculated for each prognostic blood marker. The discriminatory ability of different predictors was assessed, by calculating area under the receiver operating characteristic curves (AUC). Prognostic models including the three parameters with the best performance were identified.Results
Of 383 patients, 66 (17.2%) developed an infection after onset of stroke. WBC, CRP, copeptin and PCT were all independent predictors of any infection, pneumonia and UTI developed at least 24 hours after measurements. The combination of the biomarkers WBC, CRP and copeptin (AUC: 0.92) and WBC, CRP and PCT (AUC: 0.90) showed a better predictive accuracy concerning the development of pneumonia during hospitalization compared to each marker by itself (p-Wald <0.0001).Conclusion
Among ischemic stroke patients, copeptin, PCT, WBC and CRP measured on admission were predictors of infection in general, and specifically for pneumonia and UTI within 5 days after stroke. The combination of these biomarkers improved the prediction of patients who developed an infection. 相似文献568.
The development of the basic architecture of branching tubules enclosing a central lumen that characterizes most epithelial organs crucially depends on the apico-basolateral polarization of epithelial cells. Signals from the extracellular matrix control the orientation of the apical surface, so that it faces the lumen interior, opposite to cell-matrix adhesion sites. This orientation of the apical surface is thought to be intrinsically linked to the formation of single lumens. We previously demonstrated in three-dimensional cyst cultures of Madin-Darby canine kidney (MDCK) cells that signaling by β1 integrins regulates the orientation of the apical surface, via a mechanism that depends on the activity of the small GTPase Rac1. Here, we investigated whether the Rac1 effector Pak1 is a downstream effector in this pathway. Expression of constitutive active Pak1 phenocopies the effect of β1 integrin inhibition in that it misorients the apical surface and induces a multilumen phenotype. The misorientation of apical surfaces depends on the interaction of active Pak1 with PIX proteins and is linked to defects in basement membrane assembly. In contrast, the multilumen phenotype was independent of PIX and the basement membrane. Therefore, Pak1 likely regulates apical polarization and lumen formation by two distinct pathways. 相似文献
569.
570.
Wijngaard CC Asten Lv Koopmans MP Pelt Wv Nagelkerke NJ Wielders CC Lier Av Hoek Wv Meijer A Donker GA Dijkstra F Harmsen C Sande MA Kretzschmar M 《PloS one》2012,7(2):e31197