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101.
Wickström D Wagner S Baars L Ytterberg AJ Klepsch M van Wijk KJ Luirink J de Gier JW 《The Journal of biological chemistry》2011,286(6):4598-4609
Thus far, the role of the Escherichia coli signal recognition particle (SRP) has only been studied using targeted approaches. It has been shown for a handful of cytoplasmic membrane proteins that their insertion into the cytoplasmic membrane is at least partially SRP-dependent. Furthermore, it has been proposed that the SRP plays a role in preventing toxic accumulation of mistargeted cytoplasmic membrane proteins in the cytoplasm. To complement the targeted studies on SRP, we have studied the consequences of the depletion of the SRP component Fifty-four homologue (Ffh) in E. coli using a global approach. The steady-state proteomes and the proteome dynamics were evaluated using one- and two-dimensional gel analysis, followed by mass spectrometry-based protein identification and immunoblotting. Our analysis showed that depletion of Ffh led to the following: (i) impaired kinetics of the biogenesis of the cytoplasmic membrane proteome; (ii) lowered steady-state levels of the respiratory complexes NADH dehydrogenase, succinate dehydrogenase, and cytochrome bo(3) oxidase and lowered oxygen consumption rates; (iii) increased levels of the chaperones DnaK and GroEL at the cytoplasmic membrane; (iv) a σ(32) stress response and protein aggregation in the cytoplasm; and (v) impaired protein synthesis. Our study shows that in E. coli SRP-mediated protein targeting is directly linked to maintaining protein homeostasis and the general fitness of the cell. 相似文献
102.
Richard van den Broek Dirk‐Jan Treffers Marieke Meeusen Ad van Wijk Evert Nieuwlaar Wim Turkenburg 《Journal of Industrial Ecology》2001,5(3):65-87
Bioenergy has a large worldwide potential in future climate change abatement, although its application may become limited by demands for land for other functions. The aim of this study was to make an environmental assessment of the use of energy crops in the Netherlands in a context that incorporates scarcity of land.
A base case system was defined, consisting of conventional winter wheat production, set-aside land (1 hectare, together), and the production of coal-based electricity. Using life-cycle assessment, we compared this system with (1) a green energy system in which willow is cultivated on the set-aside land to replace the coal-based electricity and (2) an organic agriculture system in which the full hectare produces wheat under the Dutch EKO organic agriculture standard. In this way, the functional unit and the amount of land used is the same in each system. The final system comparison was based on normalized scores per environmental theme.
The green energy system scored the best with respect to acidification, climate change, and energy carrier depletion. The organic food system scored best on terrestrial eco-toxicity and slightly better on the mutually related themes of seawater and seawater sediment eco-toxicity. The base case system performed slightly better with regard to eutrophication.
Preferences, from an environmental point of view, for one of the systems should be determined by environmental policy priorities and the severity of local environmental problems. The case studied here shows that when climate change, energy carrier depletion, and acidification are the main drivers behind environmental policy, one should focus not on the extensification of agriculture, but rather dedicate more land to energy crops. Extensification of agriculture would be the preferred system when toxicity from pesticides is considered the main problem. 相似文献
A base case system was defined, consisting of conventional winter wheat production, set-aside land (1 hectare, together), and the production of coal-based electricity. Using life-cycle assessment, we compared this system with (1) a green energy system in which willow is cultivated on the set-aside land to replace the coal-based electricity and (2) an organic agriculture system in which the full hectare produces wheat under the Dutch EKO organic agriculture standard. In this way, the functional unit and the amount of land used is the same in each system. The final system comparison was based on normalized scores per environmental theme.
The green energy system scored the best with respect to acidification, climate change, and energy carrier depletion. The organic food system scored best on terrestrial eco-toxicity and slightly better on the mutually related themes of seawater and seawater sediment eco-toxicity. The base case system performed slightly better with regard to eutrophication.
Preferences, from an environmental point of view, for one of the systems should be determined by environmental policy priorities and the severity of local environmental problems. The case studied here shows that when climate change, energy carrier depletion, and acidification are the main drivers behind environmental policy, one should focus not on the extensification of agriculture, but rather dedicate more land to energy crops. Extensification of agriculture would be the preferred system when toxicity from pesticides is considered the main problem. 相似文献
103.
The CD28/CTLA-4-B7 signaling pathway is involved in both allergic sensitization and tolerance induction to orally administered peanut proteins 总被引:1,自引:0,他引:1
van Wijk F Nierkens S de Jong W Wehrens EJ Boon L van Kooten P Knippels LM Pieters R 《Journal of immunology (Baltimore, Md. : 1950)》2007,178(11):6894-6900
Dendritic cells are believed to play an essential role in regulating the balance between immunogenic and tolerogenic responses to mucosal Ags by controlling T cell differentiation and activation via costimulatory and coinhibitory signals. The CD28/CTLA-4-CD80/CD86 signaling pathway appears to be one of the most important regulators of T cell responses but its exact role in responses to orally administered proteins remains to be elucidated. In the present study, the involvement of the CD28/CTLA-4-CD80/CD86 costimulatory pathway in the induction of allergic sensitization and oral tolerance to peanut proteins was investigated. In both an established C3H/HeOuJ mouse model of peanut hypersensitivity and an oral tolerance model to peanut, CD28/CTLA-4-CD80/CD86 interactions were blocked using the fusion protein CTLA-4Ig. To examine the relative contribution of CD80- and CD86-mediated costimulation in these models, anti-CD80 and anti-CD86 blocking Abs were used. In the hypersensitivity model, CTLA-4Ig treatment prevented the development of peanut extract-induced cytokine responses, peanut extract-specific IgG1, IgG2a, and IgE production and peanut extract-induced challenge responses. Blocking of CD80 reduced, whereas anti-CD86 treatment completely inhibited, the induction of peanut extract-specific IgE. Normal tolerance induction to peanut extract was found following CTLA-4Ig, anti-CD86, or anti-CD80 plus anti-CD86 treatment, whereas blockade of CD80 impaired the induction of oral tolerance. We show that CD28/CTLA-4-CD80/CD86 signaling is essential for the development of allergic responses to peanut and that CD86 interaction is most important in inducing peanut extract-specific IgE responses. Additionally, our data suggest that CD80 but not CD86 interaction with CTLA-4 is crucial for the induction of low dose tolerance to peanut. 相似文献
104.
van Wijk HJ Harlizius B Liefers SC Buschbell H Dibbits B Groenen MA 《Animal biotechnology》2007,18(4):251-261
Marker density of a QTL region on pig chromosome 4 was increased. New microsatellites were identified by in silico mining of BAC-end and genomic shotgun sequences. Among 8,784 BAC-end sequences predicted within the region, 148 microsatellites were identified. In addition, 27,450 CA/TG repeats were identified within the genomic shotgun sequences, of which 157 were most likely located on SSC4q. A selection of 61 new microsatellites was mapped, together with previously mapped markers. The results showed that the human-pig comparative map in combination with BAC-end and genomic sequence resources provides an excellent source for a highly efficient and targeted development of markers. 相似文献
105.
106.
Posttranslational modifications (PTMs) of proteins greatly expand proteome diversity, increase functionality, and allow for rapid responses, all at relatively low costs for the cell. PTMs play key roles in plants through their impact on signaling, gene expression, protein stability and interactions, and enzyme kinetics. Following a brief discussion of the experimental and bioinformatics challenges of PTM identification, localization, and quantification (occupancy), a concise overview is provided of the major PTMs and their (potential) functional consequences in plants, with emphasis on plant metabolism. Classic examples that illustrate the regulation of plant metabolic enzymes and pathways by PTMs and their cross talk are summarized. Recent large-scale proteomics studies mapped many PTMs to a wide range of metabolic functions. Unraveling of the PTM code, i.e. a predictive understanding of the (combinatorial) consequences of PTMs, is needed to convert this growing wealth of data into an understanding of plant metabolic regulation.The primary amino acid sequence of proteins is defined by the translated mRNA, often followed by N- or C-terminal cleavages for preprocessing, maturation, and/or activation. Proteins can undergo further reversible or irreversible posttranslational modifications (PTMs) of specific amino acid residues. Proteins are directly responsible for the production of plant metabolites because they act as enzymes or as regulators of enzymes. Ultimately, most proteins in a plant cell can affect plant metabolism (e.g. through effects on plant gene expression, cell fate and development, structural support, transport, etc.). Many metabolic enzymes and their regulators undergo a variety of PTMs, possibly resulting in changes in oligomeric state, stabilization/degradation, and (de)activation (Huber and Hardin, 2004), and PTMs can facilitate the optimization of metabolic flux. However, the direct in vivo consequence of a PTM on a metabolic enzyme or pathway is frequently not very clear, in part because it requires measurements of input and output of the reactions, including flux through the enzyme or pathway. This Update will start out with a short overview on the major PTMs observed for each amino acid residue (PTMs, including determination of the localization within proteins (i.e. the specific residues) and occupancy. Challenges in dealing with multiple PTMs per protein and cross talk between PTMs will be briefly outlined. We then describe the major physiological PTMs observed in plants as well as PTMs that are nonenzymatically induced during sample preparation (PTMs, in particular for enzymes in primary metabolism (Calvin cycle, glycolysis, and respiration) and the C4 shuttle accommodating photosynthesis in C4 plants (PTMs observed in plants
Open in a separate window
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Open in a separate windowThere are many recent reviews focusing on specific PTMs in plant biology, many of which are cited in this Update. However, the last general review on plant PTMs is from 2010 (Ytterberg and Jensen, 2010); given the enormous progress in PTM research in plants over the last 5 years, a comprehensive overview is overdue. Finally, this Update does not review allosteric regulation by metabolites or other types of metabolic feedback and flux control, even if this is extremely important in the regulation of metabolism and (de)activation of enzymes. Recent reviews for specific pathways, such as isoprenoid metabolism (Kötting et al., 2010; Banerjee and Sharkey, 2014; Rodríguez-Concepción and Boronat, 2015), tetrapyrrole metabolism (Brzezowski et al., 2015), the Calvin-Benson cycle (Michelet et al., 2013), starch metabolism (Kötting et al., 2010; Geigenberger, 2011; Tetlow and Emes, 2014), and photorespiration (Hodges et al., 2013) provide more in-depth discussions of metabolic regulation through various posttranslational mechanisms. Many of the PTMs that have been discovered in the last decade through large-scale proteomics approaches have not yet been integrated in such pathway-specific reviews, because these data are not always easily accessible and because the biological significance of many PTMs is simply not yet understood. We hope that this Update will increase the general awareness of the existence of these PTM data sets, such that their biological significance can be tested and incorporated in metabolic pathways. 相似文献
Amino Acid Residue | Observed Physiological PTM in Plants | PTMs Caused by Sample Preparation |
---|---|---|
Ala (A) | Not known | |
Arg (R) | Methylation, carbonylation | |
Asn (N) | Deamidation, N-linked gycosylation | Deamidation |
Asp (D) | Phosphorylation (in two-component system) | |
Cys (C) | Glutathionylation (SSG), disulfide bonded (S-S), sulfenylation (-SOH), sulfonylation (-SO3H), acylation, lipidation, acetylation, nitrosylation (SNO), methylation, palmitoylation, phosphorylation (rare) | Propionamide |
Glu (E) | Carboxylation, methylation | Pyro-Glu |
Gln (Q) | Deamidation | Deamidation, pyro-Glu |
Gly (G) | N-Myristoylation (N-terminal Gly residue) | |
His (H) | Phosphorylation (infrequent) | Oxidation |
Ile (I) | Not known | |
Leu (L) | Not known | |
Lys (K) | N-ε-Acetylation, methylation, hydroxylation, ubiquitination, sumoylation, deamination, O-glycosylation, carbamylation, carbonylation, formylation | |
Met (M) | (De)formylation, excision (NME), (reversible) oxidation, sulfonation (-SO2), sulfoxation (-SO) | Oxidation, 2-oxidation, formylation, carbamylation |
Phe (F) | Not known | |
Pro (P) | Carbonylation | Oxidation |
Ser (S) | Phosphorylation, O-linked glycosylation, O-linked GlcNAc (O-GlcNAc) | Formylation |
Thr (T) | Phosphorylation, O-linked glycosylation, O-linked GlcNAc (O-GlcNAc), carbonylation | Formylation |
Trp (W) | Glycosylation (C-mannosylation) | Oxidation |
Tyr (Y) | Phosphorylation, nitration | |
Val (V) | Not known | |
Free NH2 of protein N termini | Preprotein processing, Met excision, formylation, pyro-Glu, N-myristoylation, N-acylation (i.e. palmitoylation), N-terminal α-amine acetylation, ubiquitination | Formylation (Met), pyro-Glu (Gln) |
Table II.
Most significant and/or frequent PTMs observed in plantsType of PTM (Reversible, Except if Marked with an Asterisk) | Spontaneous (S; Nonenzymatic) or Enzymatic (E) | Comment on Subcellular Location and Frequency |
---|---|---|
Phosphorylation (Ser, Thr, Tyr, His, Asp) | E | His and Asp phosphorylation have low frequency |
S-Nitrosylation (Cys) and nitration* (Tyr) | S (RNS), but reversal is enzymatic for Cys by thioredoxins | Throughout the cell |
Acetylation (N-terminal α-amine, Lys ε-amine) | E | In mitochondria, very little N-terminal acetylation, but high Lys acetylation; Lys acetylation correlates to [acetyl-CoA] |
Deamidation (Gln, Asn) | S, but reversal of isoAsp is enzymatic by isoAsp methyltransferase | Throughout the cell |
Lipidation (S-acetylation, N-meristoylation*, prenylation*; Cys, Gly, Lys, Trp, N terminal) | E | Not (or rarely) within plastids, mitochondria, peroxisomes |
N-Linked glycosylation (Asp); O linked (Lys, Ser, Thr, Trp) | E | Only proteins passing through the secretory system; O linked in the cell wall |
Ubiquination (Lys, N terminal) | E | Not within plastids, mitochondria, peroxisomes |
Sumoylation (Lys) | E | Not within plastids, mitochondria, peroxisomes |
Carbonylation* (Pro, Lys, Arg, Thr) | S (ROS) | High levels in mitochondria and chloroplast |
Methylation (Arg, Lys, N terminal) | E | Histones (nucleus) and chloroplasts; still underexplored |
Glutathionylation (Cys) | E | High levels in chloroplasts |
Oxidation (Met, Cys) | S (ROS) and E (by PCOs; see Fig. 1B), but reversal is enzymatic by Met sulfoxide reductases, glutaredoxins, and thioredoxins, except if double oxidized | High levels in mitochondria and chloroplast |
Peptidase* (cleavage peptidyl bond) | E | Throughout the cell |
S-Guanylation (Cys) | S (RNS) | Rare; 8-nitro-cGMP is signaling molecule in guard cells |
Formylation (Met) | S, but deformylation is enzymatic by peptide deformylase | All chloroplasts and mitochondria-encoded proteins are synthesized with initiating formylated Met |
Table III.
Regulation by PTMs in plant metabolism and classic examples of well-studied enzymes and pathwaysMany of these enzymes also undergo allosteric regulation through cellular metabolites. GAPDH, Glyceraldehyde-3-phosphate dehydrogenase; PRK, phosphoribulokinase.Process | Enzymes | PTMs, Protein Modifiers, Localization | References |
---|---|---|---|
Calvin-Benson cycle (chloroplasts) | Many enzymes | Oxidoreduction of S-S bonds, reversible nitrosylation, glutathionylation; through ferredoxin/ferredoxin-thioredoxin reductase/thioredoxins (mostly f and m) and glutaredoxins; proteomics studies in Arabidopsis and C. reinhardtii | Michelet et al. (2013) |
Rubisco | Methylation, carbamylation, acetylation, N-terminal processing, oligomerization; classical studies in pea (Pisum sativum), spinach (Spinacia oleracea), and Arabidopsis | Houtz and Portis (2003); Houtz et al. (2008) | |
GAPDH/CP12/PRK supercomplex | Dynamic heterooligomerization through reversible S-S bond formation controlled by thioredoxins | Graciet et al. (2004); Michelet et al. (2013); López-Calcagno et al. (2014) | |
Glycolysis | Cytosolic PEPC | Phosphorylation (S, T), monoubiquitination | O’Leary et al. (2011) |
Photorespiration | Seven enzymes are phosphorylated | Phosphorylation from meta-analysis of public phosphoproteomics data for Arabidopsis; located in chloroplasts, peroxisomes, mitochondria | Hodges et al. (2013) |
Maize glycerate kinase | Redox-regulated S-S bond; thioredoxin f; studied extensively in chloroplasts of C4 maize | Bartsch et al. (2010) | |
Respiration (mitochondria) | Potentially many enzymes, but functional/biochemical consequences are relatively unexplored | Recent studies suggested PTMs for many tricarboxylic acid cycle enzymes, including Lys acetylation and thioredoxin-driven S-S formation; in particular, succinate dehydrogenase and fumarase are inactivated by thioredoxins | Lázaro et al. (2013); Schmidtmann et al. (2014); Daloso et al. (2015) |
PDH | Ser (de)phosphorylation by intrinsic kinase and phosphatase; ammonia and pyruvate control PDH kinase activity; see Figure 1B | Thelen et al. (2000); Tovar-Méndez et al. (2003) | |
C4 cycle (C3 and C4 homologs also involved in glycolysis and/or gluconeogenesis) | Pyruvate orthophosphate dikinase | Phosphorylation by pyruvate orthophosphate dikinase-RP, an S/T bifunctional kinase-phosphatase; in chloroplasts | Chastain et al. (2011); Chen et al. (2014) |
PEPC | Phosphorylation; allosteric regulation by malate and Glc-6-P; in cytosol in mesophyll cells in C4 species (e.g. Panicum maximum); see Figure 1A | Izui et al. (2004); Bailey et al. (2007) | |
PEPC kinase | Ubiquitination resulting in degradation (note also diurnal mRNA levels and linkage to activity level; very low protein level); in cytosol in mesophyll cells in C4 species (e.g. Flaveria spp. and maize) | Agetsuma et al. (2005) | |
PEPC kinase | Phosphorylation in cytosol in bundle sheath cells | Bailey et al. (2007) | |
Starch metabolism (chloroplasts) | ADP-Glc pyrophosphorylase | Redox-regulated disulfide bonds and dynamic oligomerization; thioredoxins; see Figure 1C | Geigenberger et al. (2005); Geigenberger (2011) |
Starch-branching enzyme II | Phosphorylation by Ca2+-dependent protein kinase; P-driven heterooligomerization | Grimaud et al. (2008); Tetlow and Emes (2014) | |
Suc metabolism (cytosol) | SPS (synthesis of Suc) | (De)phosphorylation; SPS kinase and SPS phosphatase; 14-3-3 proteins; cytosol (maize and others) | Huber (2007) |
Suc synthase (breakdown of Suc) | Phosphorylation; Ca2+-dependent protein kinase; correlations to activity, localization, and turnover | Duncan and Huber (2007); Fedosejevs et al. (2014) | |
Photosynthetic electron transport (chloroplast thylakoid membranes) | PSII core and light-harvesting complex proteins | (De)phosphorylation by state-transition kinases (STN7/8) and PP2C phosphatases (PBCP and PPH1/TAP38) | Pesaresi et al. (2011); Tikkanen et al. (2012); Rochaix (2014) |
Nitrogen assimilation | Nitrate reductase | (De)phosphorylation; 14-3-3 proteins | Lillo et al. (2004); Huber (2007) |
107.
Huib de Jong Eva C. Koffeman Jennifer M. Meerding Rianne C. Scholman Lotte Wieten Wilco de Jager Mark Klein Henny Otten Femke van Wijk Ruurd van der Zee Johannes W. J. Bijlsma Femke Broere Willem van Eden Berent J. Prakken 《Cell stress & chaperones》2014,19(4):569-578
Self-reactive T cells have shown to have a potential role as regulators of the immune system preventing or even suppressing autoimmunity. One of the most abundant proteins that can be eluted from human HLA molecules is heat shock protein 70 (HSP70). The aims of the current study are to identify HSP70 epitopes based on published HLA elution studies and to investigate whether T cells from healthy individuals may respond to such self-epitopes. A literature search and subsequent in silico binding prediction based on theoretical MHC binding motifs resulted in the identification of seven HSP70 epitopes. PBMCs of healthy controls proliferated after incubation with two of the seven peptides (H167 and H290). Furthermore H161, H290, and H443 induced CD69 expression or production of cytokines IFNγ or TNFα in healthy controls. The identification of these naturally presented epitopes and the response they elicit in the normal immune system make them potential candidates to study during inflammatory conditions as well as in autoimmune diseases. 相似文献
108.
Sjoerd J. L. van Wijk Adrien S. J. Melquiond Sjoerd J. de Vries H. Th. Marc Timmers Alexandre M. J. J. Bonvin 《PLoS computational biology》2012,8(11)
Ubiquitination relies on a subtle balance between selectivity and promiscuity achieved through specific interactions between ubiquitin-conjugating enzymes (E2s) and ubiquitin ligases (E3s). Here, we report how a single aspartic to glutamic acid substitution acts as a dynamic switch to tip the selectivity balance of human E2s for interaction toward E3 RING-finger domains. By combining molecular dynamic simulations, experimental yeast-two-hybrid screen of E2-E3 (RING) interactions and mutagenesis, we reveal how the dynamics of an internal salt-bridge network at the rim of the E2-E3 interaction surface controls the balance between an “open”, binding competent, and a “closed”, binding incompetent state. The molecular dynamic simulations shed light on the fine mechanism of this molecular switch and allowed us to identify its components, namely an aspartate/glutamate pair, a lysine acting as the central switch and a remote aspartate. Perturbations of single residues in this network, both inside and outside the interaction surface, are sufficient to switch the global E2 interaction selectivity as demonstrated experimentally. Taken together, our results indicate a new mechanism to control E2-E3 interaction selectivity at an atomic level, highlighting how minimal changes in amino acid side-chain affecting the dynamics of intramolecular salt-bridges can be crucial for protein-protein interactions. These findings indicate that the widely accepted sequence-structure-function paradigm should be extended to sequence-structure-dynamics-function relationship and open new possibilities for control and fine-tuning of protein interaction selectivity. 相似文献
109.
In contrast to lower vertebrates, the mammalian heart has a very limited regenerative capacity. Cardiomyocytes, lost after ischemia, are replaced by fibroblasts. Although the human heart is able to form new cardiomyocytes throughout its lifespan, the efficiency of this phenomenon is not enough to substitute sufficient myocardial mass after an infarction. In contrast, zebrafish hearts regenerate through epicardial activation and initiation of myocardial proliferation. With this study we obtain insights into the activation and cellular contribution of the mammalian epicardium in response to ischemia. In a mouse myocardial infarction model we analyzed the spatio-temporal changes in expression of embryonic epicardial, EMT, and stem cell markers and the contribution of cells of the Wt1-lineage to the infarcted area. Though the integrity of the epicardial layer overlaying the infarct is lost immediately after the induction of the ischemia, it was found to be regenerated at three days post infarction. In this regenerated epicardium, the embryonic gene program is transiently re-expressed as well as proliferation. Concomitant with this activation, Wt1-lineage positive subepicardial mesenchyme is formed until two weeks post-infarction. These mesenchymal cells replace the cardiomyocytes lost due to the ischemia and contribute to the fibroblast population, myofibroblasts and coronary endothelium in the infarct, and later also to the cardiomyocyte population. We show that in mice, as in lower vertebrates, an endogenous, epicardium-dependent regenerative response to injury is induced. Although this regenerative response leads to the formation of new cardiomyocytes, their number is insufficient in mice but sufficient in lower vertebrates to replace lost cardiomyocytes. These molecular and cellular analyses provide basic knowledge essential for investigations on the regeneration of the mammalian heart aiming at epicardium-derived cells. 相似文献
110.
de Jong PR Schadenberg AW van den Broek T Beekman JM van Wijk F Coffer PJ Prakken BJ Jansen NJ 《PloS one》2012,7(4):e35070