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Article ; Online: AMPK activation enhances osteoblast differentiation on a titanium disc via autophagy.

Egashira, Kei / Kajiya, Hiroshi / Tsutsumi, Takashi / Taniguchi, Yusuke / Kakura, Kae / Ohno, Jun / Kido, Hirofumi

International journal of implant dentistry

2024 Volume 10, Issue 1, Page(s) 2

Abstract: Purpose: The acquisition of osseointegration during implant therapy is slower and poorer in patients with diabetes compared with healthy persons. The serum concentration of adiponectin in patients with type II diabetes is lower than that of healthy ... ...

Abstract	Purpose: The acquisition of osseointegration during implant therapy is slower and poorer in patients with diabetes compared with healthy persons. The serum concentration of adiponectin in patients with type II diabetes is lower than that of healthy persons via the suppression of AMP-activated protein kinase (AMPK). Therefore, we hypothesized that the AMPK activation enhances bone formation around implants, resulting in the improved acquisition of osseointegration. The purpose of this study was to evaluate the impact of AMPK activation on osteoblast differentiation and its mechanism of downstream signaling on titanium disc (Ti). Methods: Confluent mouse pre-osteoblasts (MC3T3-E1) cells (1 × 10 Results: Although the proliferation rate of osteoblasts was not different between a Ti and a tissue culture polystyrene dish, the addition of AICAR, AMPK activator slightly enhanced osteoblast proliferation on the Ti. AICAR enhanced the BMP-2-dependent transcriptional activity on the Ti, leading to upregulation in the expression of osteogenesis-associated molecules. AICAR simultaneously upregulated the expression of autophagy-associated molecules on the Ti, especially LC3-II. AdipoRon, an adiponectin receptor type1/type2 activator activated AMPK, and upregulated osteogenesis-associated molecules on Ti. Conclusions: AMPK activation enhances osteoblast differentiation on a Ti via autophagy, suggesting that it promotes the acquisition of osseointegration during implant therapy.
MeSH term(s)	Humans ; Mice ; Animals ; Osteogenesis/genetics ; AMP-Activated Protein Kinases/genetics ; AMP-Activated Protein Kinases/metabolism ; AMP-Activated Protein Kinases/pharmacology ; Titanium/pharmacology ; Titanium/metabolism ; Diabetes Mellitus, Type 2/metabolism ; Dental Implants ; Osteoblasts/metabolism ; Autophagy
Chemical Substances	AMP-Activated Protein Kinases (EC 2.7.11.31) ; Titanium (D1JT611TNE) ; Dental Implants
Language	English
Publishing date	2024-01-29
Publishing country	Germany
Document type	Journal Article
ISSN	2198-4034
ISSN (online)	2198-4034
DOI	10.1186/s40729-024-00525-2
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Article: Calcium signaling in osteoclast differentiation and bone resorption.

Kajiya, Hiroshi

Advances in experimental medicine and biology

2012 Volume 740, Page(s) 917–932

Abstract: Calcium (Ca(2+)) signaling controls multiple cellular functions and is regulated by the release of Ca(2+) from internal stores and its entry from the extracellular fluid. Ca(2+) signals in osteoclasts are essential for diverse cellular functions ... ...

Abstract	Calcium (Ca(2+)) signaling controls multiple cellular functions and is regulated by the release of Ca(2+) from internal stores and its entry from the extracellular fluid. Ca(2+) signals in osteoclasts are essential for diverse cellular functions including differentiation, bone resorption and gene transcription. Recent studies have highlighted the importance of intracellular Ca(2+) signaling for osteoclast differentiation. Receptor activator of NF-κB ligand (RANKL) signaling induces oscillatory changes in intracellular Ca(2+) concentrations, resulting in Ca(2+)/calcineurin-dependent dephosphorylation and activation of nuclear factor of activated T cells c1 (NFATc1), which translocates to the nucleus and induces osteoclast-specific gene transcription to allow differentiation of osteoclasts. Recently, some reports indicated that RANKL-induced Ca(2+) oscillation involved not only repetitive intracellular Ca(2+) release from inositol 1, 4, 5-triphosphate channels in Ca(2+) store sites, but also via store-operated Ca(2+) entry and Ca(2+) entry via transient receptor potential V channels during osteoclast differentiation. Ca(2+)-regulatory cytokines and elevation of extracellular Ca(2+) concentrations have been shown to increase intracellular Ca(2+) concentrations ([Ca(2+)](i)) in mature osteoclasts, regulating diverse cellular functions. RANKL-induced [Ca(2+)](i) increase has been reported to inhibit cell motility and the resorption of cytoskeletal structures in mature osteoclasts, resulting in suppression of bone-resorption activity. In conclusion, Ca(2+) signaling activates differentiation in osteoclast precursors but suppresses resorption in mature osteoclasts. This chapter focuses on the roles of long-term Ca(2+) oscillations in differentiation and of short-term Ca(2+) increase in osteoclastic bone resorption activity.
MeSH term(s)	Animals ; Bone Resorption/etiology ; Calcium/metabolism ; Calcium Channels/physiology ; Calcium Signaling/physiology ; Cell Differentiation ; Cell Movement ; Humans ; NFATC Transcription Factors/physiology ; Osteoclasts/cytology ; TRPV Cation Channels/physiology
Chemical Substances	Calcium Channels ; NFATC Transcription Factors ; TRPV Cation Channels ; Trpv5 protein, mouse ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2012
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ISSN	2214-8019 ; 0065-2598
ISSN (online)	2214-8019
ISSN	0065-2598
DOI	10.1007/978-94-007-2888-2_41
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Article ; Online: Corrigendum to "Three-dimensional spheroids of mesenchymal stem/stromal cells promote osteogenesis by activating stemness and Wnt/β-catenin".

Imamura, Ayaka / Kajiya, Hiroshi / Fujisaki, Seiichi / Maeshiba, Munehisa / Yanagi, Tsukasa / Kojima, Hiroshi / Ohno, Jun

Biochemical and biophysical research communications

2020 Volume 524, Issue 1, Page(s) 272

Language	English
Publishing date	2020-02-19
Publishing country	United States
Document type	Journal Article ; Published Erratum
ZDB-ID	205723-2
ISSN	1090-2104 ; 0006-291X ; 0006-291X
ISSN (online)	1090-2104 ; 0006-291X
ISSN	0006-291X
DOI	10.1016/j.bbrc.2020.02.097
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Article ; Online: Conditional knockout of transient receptor potential melastatin 7 in the enamel epithelium: Effects on enamel formation.

Shin, Masashi / Matsushima, Aya / Kajiya, Hiroshi / Okamoto, Fujio / Ogata, Kayoko / Oka, Kyoko / Ohshima, Hayato / Bartlett, John D / Okabe, Koji

European journal of oral sciences

2023 Volume 131, Issue 2, Page(s) e12920

Abstract: Transient receptor potential melastatin 7 (TRPM7) is a unique ion channel connected to a kinase domain. We previously demonstrated that Trpm7 expression is high in mouse ameloblasts and odontoblasts, and that amelogenesis is impaired in TRPM7 kinase-dead ...

Abstract	Transient receptor potential melastatin 7 (TRPM7) is a unique ion channel connected to a kinase domain. We previously demonstrated that Trpm7 expression is high in mouse ameloblasts and odontoblasts, and that amelogenesis is impaired in TRPM7 kinase-dead mice. Here, we analyzed TRPM7 function during amelogenesis in Keratin 14-Cre;Trpm7
MeSH term(s)	Mice ; Rats ; Animals ; TRPM Cation Channels/genetics ; TRPM Cation Channels/metabolism ; Mice, Knockout ; Dental Enamel/metabolism ; Ameloblasts/metabolism ; Epithelium ; Amelogenesis/genetics ; Carrier Proteins/metabolism ; Incisor
Chemical Substances	TRPM Cation Channels ; Carrier Proteins ; Trpm7 protein, mouse (EC 2.7.1.-) ; Trpm7 protein, rat (EC 2.7.11.1)
Language	English
Publishing date	2023-02-16
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1224820-4
ISSN	1600-0722 ; 0909-8836
ISSN (online)	1600-0722
ISSN	0909-8836
DOI	10.1111/eos.12920
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Article ; Online: Usefulness of Serum Leucine-Rich Alpha-2 Glycoprotein as a Surrogate Marker of Small Bowel Mucosal Injury in Crohn's Disease.

Saiki, Takuto / Torisu, Takehiro / Harada, Akira / Kajiya, Yu / Taniguchi, Yoshiaki / Morisaki, Shinji / Umeno, Junji / Suekane, Hiroshi / Kitazono, Takanari

Inflammatory intestinal diseases

2023 Volume 8, Issue 2, Page(s) 69–76

Abstract: Introduction: Although the importance of mucosal healing has been suggested in Crohn's disease, it is difficult to repeat endoscopy, especially for the entire small bowel. Recently, serum leucine-rich alpha-2 glycoprotein (LRG) has been used as a ... ...

Abstract	Introduction: Although the importance of mucosal healing has been suggested in Crohn's disease, it is difficult to repeat endoscopy, especially for the entire small bowel. Recently, serum leucine-rich alpha-2 glycoprotein (LRG) has been used as a surrogate marker of endoscopy. However, few studies have investigated a correlation between LRG and mucosal injury of the entire small bowel. Methods: We retrospectively analyzed the clinical data of 30 patients with Crohn's disease from June 2020 to August 2022 at Yamaguchi Red Cross Hospital. All the patients were surveyed through the gastrointestinal tract by esophagogastroduodenoscopy, total colonoscopy, and capsule endoscopy (CE). Subjects with mucosal injury only in the small bowel were selected. Then, we assessed the relationship between serum biomarkers (LRG, C-reactive protein [CRP], hemoglobin, albumin) and small bowel mucosal injury scores (Lewis score [LS], Capsule Endoscopy Crohn's Disease Activity Index [CECDAI], and Crohn's Disease Activity in Capsule Endoscopy [CDACE]) calculated by CE. Results: LRG and CRP were significantly correlated with small bowel mucosal injury scores (LS, CECDAI, CDACE) ( Conclusions: LRG is a useful surrogate marker that closely reflects small bowel mucosal injury in the entire small bowel.
Language	English
Publishing date	2023-07-10
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2817967-5
ISSN	2296-9365 ; 2296-9365
ISSN (online)	2296-9365
ISSN	2296-9365
DOI	10.1159/000531622
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Article ; Online: Corrigendum to "Three-dimensional spheroids of mesenchymal stem/stromal cells promote osteogenesis by activating stemness and Wnt/β-catenin" [Biochem Biophys Res Commun. 2020 523(2) 458-464].

Imamura, Ayaka / Kajiya, Hiroshi / Fujisaki, Seiichi / Maeshiba, Munehisa / Yanagi, Tsukasa / Kojima, Hiroshi / Ohno, Jun

Biochemical and biophysical research communications

2020 Volume 525, Issue 3, Page(s) 819–820

Language	English
Publishing date	2020-03-07
Publishing country	United States
Document type	Published Erratum
ZDB-ID	205723-2
ISSN	1090-2104 ; 0006-291X ; 0006-291X
ISSN (online)	1090-2104 ; 0006-291X
ISSN	0006-291X
DOI	10.1016/j.bbrc.2020.02.158
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Article ; Online: Enhancement of jaw bone regeneration via ERK1/2 activation using dedifferentiated fat cells.

Fujisaki, Seiichi / Kajiya, Hiroshi / Yanagi, Tsukasa / Maeshiba, Munehisa / Kakura, Kae / Kido, Hirofumi / Ohno, Jun

Cytotherapy

2021 Volume 23, Issue 7, Page(s) 608–616

Abstract: Background aims: Mesenchymal stem/stromal cells (MSCs) are multipotent and self-renewing cells that are extensively used in tissue engineering. Adipose tissues are known to be the source of two types of MSCs; namely, adipose tissue-derived MSCs (ASCs) ... ...

Abstract	Background aims: Mesenchymal stem/stromal cells (MSCs) are multipotent and self-renewing cells that are extensively used in tissue engineering. Adipose tissues are known to be the source of two types of MSCs; namely, adipose tissue-derived MSCs (ASCs) and dedifferentiated fat (DFAT) cells. Although ASCs are sometimes transplanted for clinical cytotherapy, the effects of DFAT cell transplantation on mandibular bone healing remain unclear. Methods: The authors assessed whether DFAT cells have osteogenerative potential compared with ASCs in rats in vitro. In addition, to elucidate the ability of DFAT cells to regenerate the jaw bone, the authors examined the effects of DFAT cells on new bone formation in a mandibular defect model in (i) 30-week-old rats and (ii) ovariectomy-induced osteoporotic rats in vivo. Results: Osteoblast differentiation with bone morphogenetic protein 2 (BMP-2) or osteogenesis-induced medium upregulated the osteogenesis-related molecules in DFAT cells compared with those in ASCs. BMP-2 activated the phosphorylation signaling pathways of ERK1/2 and Smad2 in DFAT cells, but minor Smad1/5/9 activation was noted in ASCs. The transplantation of DFAT cells into normal or ovariectomy-induced osteoporotic rats with mandibular defects promoted new bone formation compared with that seen with ASCs. Conclusions: DFAT cells promoted osteoblast differentiation and new bone formation through ERK1/2 and Smad2 signaling pathways in vitro. The transplantation of DFAT cells promoted new mandibular bone formation in vivo compared with that seen with ASCs. These results suggest that transplantation of ERK1/2-activated DFAT cells shorten the mandibular bone healing process in cytotherapy.
MeSH term(s)	Adipocytes ; Adipose Tissue ; Animals ; Bone Regeneration ; Cell Differentiation ; Female ; MAP Kinase Signaling System ; Osteogenesis ; Rats
Language	English
Publishing date	2021-04-16
Publishing country	England
Document type	Journal Article
ZDB-ID	2039821-9
ISSN	1477-2566 ; 1465-3249
ISSN (online)	1477-2566
ISSN	1465-3249
DOI	10.1016/j.jcyt.2021.02.115
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Article ; Online: Occlusal disharmony transiently decrease cognition via cognitive suppressor molecules and partially restores cognitive ability via clearance molecules.

Maeshiba, Munehisa / Kajiya, Hiroshi / Tsutsumi, Takashi / Migita, Keisuke / Goto-T, Kazuko / Kono, Yuri / Tsuzuki, Takashi / Ohno, Jun

Biochemical and biophysical research communications

2022 Volume 594, Page(s) 74–80

Abstract: Occlusal disharmony has been reported to be affected not only by cytokine and steroid hormone secretion and sympathetic activation in peripheral organs, but also by neurotransmitter release in the central nervous system. However, little is known about ... ...

Abstract	Occlusal disharmony has been reported to be affected not only by cytokine and steroid hormone secretion and sympathetic activation in peripheral organs, but also by neurotransmitter release in the central nervous system. However, little is known about whether occlusal disharmony can decrease cognitive ability. We hypothesized that hyperocclusion decreases cognition via Alzheimer's disease-associated molecule expression in the brain. The present study is aimed to elucidate the relationships among occlusal disharmony, cytokine and cognitive-regulated molecule expression in the brain, and the impairment of learning and memory cognition. We examined the effect of hyperocclusion on the relationships among cytokine expression, cognitive suppressor molecules in the hippocampus, and cognition in behavior using a hyperocclusion mouse model. Hyperocclusion dramatically increased interleukin-1β expression in the serum and hippocampus 1 week after hyperocclusal loading in 2-month-old mice, but no effects in 12-month-old mice. The social and long-term cognitive abilities of the 2-month-old mice were transiently downregulated close to the level of the 12-month-old mice 1 week after hyperocclusion and recovered to close to basal level via the expression of cognitive suppressor clearing proteins. The expression levels of amyloid-β and phosphorylated tau were significantly upregulated 1 week after hyperocclusal loading in the hippocampus of 2-month-old mice but were constant in 12-month-old mice. Occlusal disharmony-induced interleukin-1β expression may contribute to accumulation of cognitive suppressor molecules such as amyloid-β and phosphorylated tau and activate their clearance proteins, resulting in protection against transient dementia in young but not older individuals.
MeSH term(s)	Alzheimer Disease/metabolism ; Amyloid beta-Peptides/metabolism ; Animals ; Behavior, Animal ; Cognition ; Dementia/prevention & control ; Disease Models, Animal ; Hippocampus/metabolism ; Interleukin-1beta/metabolism ; Learning ; Male ; Malocclusion/genetics ; Malocclusion/metabolism ; Mice ; Mice, Inbred C57BL ; Phosphorylation ; tau Proteins/metabolism
Chemical Substances	Amyloid beta-Peptides ; IL1B protein, mouse ; Interleukin-1beta ; tau Proteins
Language	English
Publishing date	2022-01-14
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	205723-2
ISSN	1090-2104 ; 0006-291X ; 0006-291X
ISSN (online)	1090-2104 ; 0006-291X
ISSN	0006-291X
DOI	10.1016/j.bbrc.2022.01.048
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Article ; Online: Corrigendum to "Reactive oxygen species promotes cellular senescence in normal human epidermal keratinocytes through epigenetic regulation of p16(INK4a)" [Biochem. Biophys. Res. Commun. 452 (2014) 622-628].

Sasaki, Mina / Kajiya, Hiroshi / Ozeki, Satoru / Okabe, Koji / Ikebe, Tetsuro

Biochemical and biophysical research communications

2018 Volume 505, Issue 2, Page(s) 634–635

Language	English
Publishing date	2018-09-21
Publishing country	United States
Document type	Journal Article ; Published Erratum
ZDB-ID	205723-2
ISSN	1090-2104 ; 0006-291X ; 0006-291X
ISSN (online)	1090-2104 ; 0006-291X
ISSN	0006-291X
DOI	10.1016/j.bbrc.2018.09.063
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Article ; Online: Three-dimensional spheroids of mesenchymal stem/stromal cells promote osteogenesis by activating stemness and Wnt/β-catenin.

Imamura, Ayaka / Kajiya, Hiroshi / Fujisaki, Seiichi / Maeshiba, Munehisa / Yanagi, Tsukasa / Kojima, Hiroshi / Ohno, Jun

Biochemical and biophysical research communications

2019 Volume 523, Issue 2, Page(s) 458–464

Abstract: Mesenchymal stem/stromal cells (MSCs) are multipotent and self-renewal cells that are widely used in regenerative medicine. The culture of three-dimensional (3D) spheroid MSCs more accurately mimics the biological microenvironment. However, it is unclear ...

Abstract	Mesenchymal stem/stromal cells (MSCs) are multipotent and self-renewal cells that are widely used in regenerative medicine. The culture of three-dimensional (3D) spheroid MSCs more accurately mimics the biological microenvironment. However, it is unclear which key molecules are responsible for the cell fate control of MSCs during 3D spheroid formation and their impact on the functional characteristics of these stem cells. Furthermore, it remains unclear what effects 3D spheroid MSC transplantation has on new bone formation compared with that of 2D monolayer MSCs. We assessed whether the osteogenerative potential of 3D spheroid MSCs is greater than that of 2D monolayer MSCs in vitro. In addition, to elucidate the ability of 3D spheroid MSCs to regenerate bone, we examined the effects of transplanting wild-type (WT) or knockout (KO) spheroid MSCs on new bone formation in mice calvarial defect model in vitro. The 3D spheroid MSC culture dramatically upregulated into stemness markers compared with the 2D monolayer MSC culture. In contrast, BMP-2 significantly increased the osteogenesis-related molecules in the 3D spheroid MSCs but, in turn, downregulated the stemness markers. BMP-2 activated Smad1/5 together with Wnt/β-catenin in 3D spheroid MSCs. Transplantation of these MSCs into aged mice with calvarial defects promoted new bone formation compared with that of 2D monolayer MSCs. In contrast, transplantation of 3D or 2D β-catenin knockout MSCs induced little new bone formation. The 3D spheroid MSC culture had higher stemness compared with the 2D monolayer MSC culture. The culture of 3D spheroid MSCs rapidly promoted osteoblastogenesis and bone formation through synergistic activation of the Wnt/β-catenin pathway in vitro. The transformation of 3D spheroid, but not 2D monolayer, MSCs promoted new bone regeneration in vivo. These results indicate that transplantation of 3D spheroid MSCs in regeneration therapy contributes to a shorter regenerative healing process, including new bone formation.
MeSH term(s)	Animals ; Bone Morphogenetic Protein 2/genetics ; Bone Morphogenetic Protein 2/metabolism ; Cells, Cultured ; Gene Expression Regulation ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stem Cells/cytology ; Mesenchymal Stem Cells/physiology ; Mice, Knockout ; Osteogenesis/genetics ; Osteogenesis/physiology ; Protein-Serine-Threonine Kinases/metabolism ; Skull/cytology ; Skull/diagnostic imaging ; Skull/injuries ; Spheroids, Cellular ; Wnt Proteins/metabolism ; X-Ray Microtomography ; beta Catenin/genetics ; beta Catenin/metabolism
Chemical Substances	Bmp2 protein, mouse ; Bone Morphogenetic Protein 2 ; CTNNB1 protein, mouse ; Wnt Proteins ; beta Catenin ; Hippo protein, mouse (EC 2.7.11.1) ; Protein-Serine-Threonine Kinases (EC 2.7.11.1)
Language	English
Publishing date	2019-12-24
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	205723-2
ISSN	1090-2104 ; 0006-291X ; 0006-291X
ISSN (online)	1090-2104 ; 0006-291X
ISSN	0006-291X
DOI	10.1016/j.bbrc.2019.12.066
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