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991.
Argyris Tzouvelekis Vassilis Aidinis Vagelis Harokopos Andreas Karameris George Zacharis Dimitrios Mikroulis Fotios Konstantinou Paschalis Steiropoulos Ioannis Sotiriou Marios Froudarakis Ioannis Pneumatikos Rodoula Tringidou Demosthenes Bouros 《Respiratory research》2009,10(1):14
Background
Recent evidence has underscored the role of hypoxia and angiogenesis in the pathogenesis of idiopathic fibrotic lung disease. Inhibitor of growth family member 4 (ING4) has recently attracted much attention as a tumor suppressor gene, due to its ability to inhibit cancer cell proliferation, migration and angiogenesis. The aim of our study was to investigate the role of ING4 in the pathogenesis of pulmonary fibrosis both in the bleomycin (BLM)-model and in two different types of human pulmonary fibrosis, including idiopathic pulmonary fibrosis (IPF) and cryptogenic organizing pneumonia (COP).Methods
Experimental model of pulmonary fibrosis was induced by a single tail vein injection of bleomycin in 6- to 8-wk-old C57BL/6mice. Tissue microarrays coupled with qRT-PCR and immunohistochemistry were applied in whole lung samples and paraffin-embedded tissue sections of 30 patients with IPF, 20 with COP and 20 control subjects.Results
A gradual decline of ING4 expression in both mRNA and protein levels was reported in the BLM-model. ING4 was also found down-regulated in IPF patients compared to COP and control subjects. Immunolocalization analyses revealed increased expression in areas of normal epithelium and in alveolar epithelium surrounding Masson bodies, in COP lung, whereas showed no expression within areas of active fibrosis within IPF and COP lung. In addition, ING4 expression levels were negatively correlated with pulmonary function parameters in IPF patients.Conclusion
Our data suggest a potential role for ING4 in lung fibrogenesis. ING4 down-regulation may facilitate aberrant vascular remodelling and fibroblast proliferation and migration leading to progressive disease. 相似文献992.
Ioannis P. Nezis Bhupendra V. Shravage Antonia P. Sagona Trond Lamark Geir Bj?rk?y Terje Johansen Tor Erik Rusten Andreas Brech Eric H. Baehrecke Harald Stenmark 《The Journal of cell biology》2010,190(4):523-531
Autophagy is an evolutionarily conserved pathway responsible for degradation of cytoplasmic material via the lysosome. Although autophagy has been reported to contribute to cell death, the underlying mechanisms remain largely unknown. In this study, we show that autophagy controls DNA fragmentation during late oogenesis in Drosophila melanogaster. Inhibition of autophagy by genetically removing the function of the autophagy genes atg1, atg13, and vps34 resulted in late stage egg chambers that contained persisting nurse cell nuclei without fragmented DNA and attenuation of caspase-3 cleavage. The Drosophila inhibitor of apoptosis (IAP) dBruce was found to colocalize with the autophagic marker GFP-Atg8a and accumulated in autophagy mutants. Nurse cells lacking Atg1 or Vps34 in addition to dBruce contained persisting nurse cell nuclei with fragmented DNA. This indicates that autophagic degradation of dBruce controls DNA fragmentation in nurse cells. Our results reveal autophagic degradation of an IAP as a novel mechanism of triggering cell death and thereby provide a mechanistic link between autophagy and cell death. 相似文献
993.
Nikolas Borompokas Maria-Martha Papachatzaki Konstantinos Kanavouras Vasileios Mastorodemos Ioannis Zaganas Cleanthe Spanaki Andreas Plaitakis 《The Journal of biological chemistry》2010,285(41):31380-31387
Mammalian glutamate dehydrogenase (GDH) is a housekeeping enzyme central to the metabolism of glutamate. Its activity is potently inhibited by GTP (IC50 = 0.1–0.3 μm) and thought to be controlled by the need of the cell in ATP. Estrogens are also known to inhibit mammalian GDH, but at relatively high concentrations. Because, in addition to this housekeeping human (h) GDH1, humans have acquired via a duplication event an hGDH2 isoform expressed in human cortical astrocytes, we tested here the interaction of estrogens with the two human isoenzymes. The results showed that, under base-line conditions, diethylstilbestrol potently inhibited hGDH2 (IC50 = 0.08 ± 0.01 μm) and with ∼18-fold lower affinity hGDH1 (IC50 = 1.67 ± 0.06 μm; p < 0.001). Similarly, 17β-estradiol showed a ∼18-fold higher affinity for hGDH2 (IC50 = 1.53 ± 0.24 μm) than for hGDH1 (IC50 = 26.94 ± 1.07 μm; p < 0.001). Also, estriol and progesterone were more potent inhibitors of hGDH2 than hGDH1. Structure/function analyses revealed that the evolutionary R443S substitution, which confers low basal activity, was largely responsible for sensitivity of hGDH2 to estrogens. Inhibition of both human GDHs by estrogens was inversely related to their state of activation induced by ADP, with the slope of this correlation being steeper for hGDH2 than for hGDH1. Also, the study of hGDH1 and hGDH2 mutants displaying different states of activation revealed that the affinity of estrogen for these enzymes correlated inversely (R = 0.99; p = 0.0001) with basal catalytic activity. Because astrocytes are known to synthesize estrogens, these hormones, by interacting potently with hGDH2 in its closed state, may contribute to regulation of glutamate metabolism in brain. 相似文献
994.
Sofia K. Mastronicolis Anita Berberi Ioannis Diakogiannis Evanthia Petrova Irene Kiaki Triantafillia Baltzi Polydoros Xenikakis 《Antonie van Leeuwenhoek》2010,98(3):307-316
This study provides a first approach to observe the effects on Listeria monocytogenes of cellular exposure to acid stress at low or neutral pH, notably how phospho- or neutral lipids are involved in this mechanism,
besides the fatty acid profile alteration. A thorough investigation of the composition of polar and neutral lipids from L. monocytogenes grown at pH 5.5 in presence of hydrochloric, acetic and lactic acids, or at neutral pH 7.3 in presence of benzoic acid, is
described relative to cells grown in acid-free medium. The results showed that only low pH values enhance the antimicrobial
activity of an acid. We suggest that, irrespective of pH, the acid adaptation response will lead to a similar alteration in
fatty acid composition [decreasing the ratio of branched chain/saturated straight fatty acids of total lipids], mainly originating
from the neutral lipid class of adapted cultures. Acid adaptation in L. monocytogenes was correlated with a decrease in total lipid phosphorus and, with the exception of cells adapted to benzoic acid, this change
in the amount of phosphorus reflected a higher content of the neutral lipid class. Upon acetic or benzoic acid stress the
lipid phosphorus proportion was analysed in the main phospholipids present: cardiolipin, phosphatidylglycerol, phosphoaminolipid
and phosphatidylinositol. Interestingly only benzoic acid had a dramatic effect on the relative quantities of these four phospholipids. 相似文献
995.
996.
Nezis IP Stravopodis DJ Margaritis LH Papassideri IS 《Development, growth & differentiation》2006,48(3):189-198
In the present study, we describe the features of programmed cell death of ovarian follicle cells, occurring during the late developmental stages of oogenesis in the olive fruit fly, Bactrocera oleae and the medfly, Ceratitis capitata. During stage 14, the follicle cells contain autophagic vacuoles, and they do not exhibit caspase activity in all parts of the egg chamber. Their nuclei are characterized by condensed chromatin, accompanied with high- but not low-molecular weight DNA fragmentation events exclusively detected in distinct cells of the anterior pole. These data argue for the presence of an autophagy-mediated cell death program in the ovarian follicle cell layer in both species. The above results are likely associated with the abundant phagocytosis observed at the entry of the lateral oviducts, where numerous cell bodies are massively engulfed by epithelial cells. We strongly believe that during the termination of the above Dipteran oogenesis, an efficient mechanism of absorption of the degenerated follicle cells is selectively activated, in order to prevent the blockage of the ovarioles and thus robustly support the physiological completion of the ovulation process. 相似文献
997.
998.
Stylianou IM Tsaih SW DiPetrillo K Ishimori N Li R Paigen B Churchill G 《Genetics》2006,174(2):999-1007
Intercrosses between inbred lines provide a traditional approach to analysis of polygenic inheritance in model organisms. Chromosome substitution strains (CSSs) have been developed as an alternative to accelerate the pace of gene identification in quantitative trait mapping. We compared a classical intercross and three CSS intercrosses to examine the genetic architecture underlying plasma high-density lipoprotein cholesterol (HDL) levels in the C57BL/6J (B) and A/J (A) mouse strains. The B x A intercross revealed significant quantitative trait loci (QTL) for HDL on chromosomes 1, 4, 8, 15, 17, 18, and 19. A CSS survey revealed that many have significantly different HDL levels compared to the background strain B, including chromosomes with no significant QTL in the intercross and, in some cases (CSS-1, CSS-17), effects that are opposite to those observed in the B x A intercross population. Intercrosses between B and three CSSs (CSS-3, CSS-11, and CSS-8) revealed significant QTL but with some unexpected differences from the B x A intercross. Our inability to predict the results of CSS intercrosses suggests that additional complexity will be revealed by further crosses and that the CSS mapping strategy should be viewed as a complement to, rather than a replacement for, classical intercross mapping. 相似文献
999.
Heteroptera species were collected from 48 sites distributed throughout the mainland and island complexes of Greece during
1999–2004. The aims of this study were to investigate Heteroptera distribution and abundance in Greek streams, identify the
environmental factors that are linked to variation in their assemblages and to partition the influence of environmental and
spatial components, alone and in combination, on Heteroptera community composition. Canonical ordination techniques (CCA)
were used to determine the relationship between environmental variables and species abundance, while variation partitioning
was performed using partial CCA to understand the importance of different explanatory variables in Heteroptera variation.
Heteroptera variation was decomposed into independent and joint effects of local (physicochemical variables, microhabitat
composition, stream width and depth), regional (land use/cover) and geographic variables (longitude, latitude, altitude and
distance to source). Land use/cover, aquatic and riparian vegetation, stream size and water chemistry were the most important
factors structuring Heteroptera assemblages. At regional scale, bug assemblages were mainly divided into those found in forested
and agricultural landscapes, following water quality and microhabitat composition at local scale. Local variables accounted
for 48% of the total explained variation, regional variables for 20% whereas geographical position appeared to be the least
influencing factor (8.5%). The results of partial constraint analyses suggested that local variables play a major role in
Heteroptera variation followed by regional variables.
Electronic supplementary material Electronic supplementary material is available for this article at
and accessible for authorised users. 相似文献
1000.