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51.
Gudzenko V Shiferaw Y Savalli N Vyas R Weiss JN Olcese R 《American journal of physiology. Heart and circulatory physiology》2007,293(3):H1805-H1815
Previous studies have demonstrated that the slope of the function relating the action potential duration (APD) and the diastolic interval, known as the APD restitution curve, plays an important role in the initiation and maintenance of ventricular fibrillation. Since the APD restitution slope critically depends on the kinetics of the L-type Ca(2+) current, we hypothesized that manipulation of the subunit composition of these channels may represent a powerful strategy to control cardiac arrhythmias. We studied the kinetic properties of the human L-type Ca(2+) channel (Ca(v)1.2) coexpressed with the alpha(2)delta-subunit alone (alpha(1C) + alpha(2)delta) or in combination with beta(2a), beta(2b), or beta(3) subunits (alpha(1C) + alpha(2)delta + beta), using Ca(2+) as the charge carrier. We then incorporated the kinetic properties observed experimentally into the L-type Ca(2+) current mathematical model of the cardiac action potential to demonstrate that the APD restitution slope can be selectively controlled by altering the subunit composition of the Ca(2+) channel. Assuming that beta(2b) most closely resembles the native cardiac L-type Ca(2+) current, the absence of beta, as well as the coexpression of beta(2a), was found to flatten restitution slope and stabilize spiral waves. These results imply that subunit modification of L-type Ca(2+) channels can potentially be used as an antifibrillatory strategy. 相似文献
52.
Masotti A Moretti F Mancini F Russo G Di Lauro N Checchia P Marianecci C Carafa M Santucci E Ortaggi G 《Bioorganic & medicinal chemistry》2007,15(3):1504-1515
Non-viral gene therapy is based on the development of efficient and safe gene carrier systems able to transfer DNA into cells. Polyethylenimine (PEI), the most promising non-viral vector, with its high cationic-charge-density potential is able (1) to compact DNA in complexes (polyplexes) smaller than those formed by liposomes (lipoplexes) and (2) to destabilize the endosomal membrane by a 'proton sponge' effect. Several PEI's hydrophobic modifications were reported in the last several years but in some cases a reduced transfection efficiency was observed. The mechanism underlying this phenomenon is not well understood so far. In order to extensively investigate these mechanisms, we reported a physicochemical and biological study of selected hydrophobic PEI's derivatives grafted with chains of different length and percentages of substitution able to form vesicles (polycationic liposomes) and to bind DNA. Their properties were studied by means of dynamic light scattering, freeze-fracture microscopy, potentiometric titrations, gel retardation assays, polyanion exchange reactions, toxicity assays, in vitro transfections, and fluorescence microscopy. Our results indicate that even if polyplexes are able to pass through the cellular membrane, the stability of PEI's hydrophobic polyplexes likely explain their different transfection efficiency in vitro. 相似文献
53.
Gagliano N Bedoni M Mantovani G Chiriva-Internati M Castelli D Torri C Donetti E 《European journal of histochemistry : EJH》2007,51(4):283-290
The early radiation of epidermal reactions can lead to healing of the lesion or radiation necrosis. There is no general agreement for either the prevention and/or treatment of radiation skin response, also as little is known about the immediate phases of this phenomenon. We investigated the early effects exerted by Healing and Wound Emulsion (HWE) on human skin response after ionizing radiation. Epidermal morphology, Heat Shock Protein (HSP) 70, and Transforming Growth Factor-beta1 (TGF-beta1) gene expression were investigated in organotypic human skin cultures undergoing a double dose of gamma-rays (2 Gy). HSP70 gene expression tended to be induced in the HWE group 6 hours after cream administration and was significantly up-regulated after 48 hours, when epidermal morphological alterations were evident. TGF-beta1 seems not affected in cream treated samples. HWE may stimulate skin to mount an early defensive response against damage induced by gamma rays. 相似文献
54.
Kim DW Chung HK Park KC Hwang JH Jo YS Chung J Kalvakolanu DV Resta N Shong M 《Molecular endocrinology (Baltimore, Md.)》2007,21(12):3039-3049
55.
Rui P Galao Nicoletta Scheller Isabel Alves-Rodrigues Tanja Breinig Andreas Meyerhans Juana Díez 《Microbial cell factories》2007,6(1):32
The yeast Saccharomyces cerevisiae is a well-established model system for understanding fundamental cellular processes relevant to higher eukaryotic organisms.
Less known is its value for virus research, an area in which Saccharomyces cerevisiae has proven to be very fruitful as well. The present review will discuss the main achievements of yeast-based studies in basic
and applied virus research. These include the analysis of the function of individual proteins from important pathogenic viruses,
the elucidation of key processes in viral replication through the development of systems that allow the replication of higher
eukayotic viruses in yeast, and the use of yeast in antiviral drug development and vaccine production. 相似文献
56.
Genovesio A Kwon YJ Windisch MP Kim NY Choi SY Kim HC Jung S Mammano F Perrin V Boese AS Casartelli N Schwartz O Nehrbass U Emans N 《Journal of biomolecular screening》2011,16(9):945-958
Recent genome-wide RNAi screens have identified >842 human genes that affect the human immunodeficiency virus (HIV) cycle. The list of genes implicated in infection differs between screens, and there is minimal overlap. A reason for this variance is the interdependence of HIV infection and host cell function, producing a multitude of indirect or pleiotropic cellular effects affecting the viral infection during RNAi screening. To overcome this, the authors devised a 15-dimensional phenotypic profile to define the viral infection block induced by CD4 silencing in HeLa cells. They demonstrate that this phenotypic profile excludes nonspecific, RNAi-based side effects and viral replication defects mediated by silencing of housekeeping genes. To achieve statistical robustness, the authors used automatically annotated RNAi arrays for seven independent genome-wide RNAi screens. This identified 56 host genes, which reliably reproduced CD4-like phenotypes upon HIV infection. The factors include 11 known HIV interactors and 45 factors previously not associated with HIV infection. As proof of concept, the authors confirmed that silencing of PAK1, Ku70, and RNAseH2A impaired HIV replication in Jurkat cells. In summary, multidimensional, visual profiling can identify genes required for HIV infection. 相似文献
57.
Blinks and saccades cause transient interruptions of visual input. To investigate how such effects influence our perceptual
state, we analyzed the time courses of blink and saccade rates in relation to perceptual switching in the Necker cube. Both
time courses of blink and saccade rates showed peaks at different moments along the switching process. A peak in blinking
rate appeared 1,000 ms prior to the switching responses. Blinks occurring around this peak were associated with subsequent
switching to the preferred interpretation of the Necker cube. Saccade rates showed a peak 150 ms prior to the switching response.
The direction of saccades around this peak was predictive of the perceived orientation of the Necker cube afterwards. Peak
blinks were followed and peak saccades were preceded by transient parietal theta band activity indicating the changing of
the perceptual interpretation. Precisely-timed blinks, therefore, can initiate perceptual switching, and precisely-timed saccades
can facilitate an ongoing change of interpretation. 相似文献
58.
Crisafulli E Beneventi C Bortolotti V Kidonias N Fabbri LM Chetta A Clini EM 《PloS one》2011,6(8):e23770
Background
Measurements of Energy Expenditure (EE) at rest (REE) and during physical activities are increasing in interest in chronic patients. In this study we aimed at evaluating the validity/reliability of the SenseWear®Armband (SWA) device in terms of REE and EE during assisted walking in Chronic Respiratory Failure (CRF) patients receiving long-term oxygen therapy (LTOT).Methodology/Principal Findings
In a two-phase prospective protocol we studied 40 severe patients and 35 age-matched healthy controls. In phase-1 we determined the validity and repeatability of REE measured by SWA (REEa) in comparison with standard calorimetry (REEc). In phase-2 we then assessed EE and Metabolic Equivalents-METs by SWA during the 6-minute walking test while breathing oxygen in both assisted (Aid) or unassisted (No-Aid) modalities. When compared with REEc, REEa was slightly lower in patients (1351±169 vs 1413±194 kcal/day respectively, p<0.05), and less repeatable than in healthy controls (0.14 and 0.43 coefficient respectively). COPD patients with CRF patients reported a significant gain with Aid as compared with No-Aid modality in terms of meters walked, perceived symptoms and EE.Conclusions/Significance
SWA provides a feasible and valid method to assess the energy expenditure in CRF patients on LTOT, and it shows that aided walking results in a substantial energy saving in this population. 相似文献59.
60.