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排序方式: 共有212条查询结果,搜索用时 703 毫秒
161.
Expression of ADAMTS homologues in articular cartilage. 总被引:4,自引:0,他引:4
162.
Gilbert AM Bursavich MG Lombardi S Georgiadis KE Reifenberg E Flannery CR Morris EA 《Bioorganic & medicinal chemistry letters》2007,17(5):1189-1192
A series of 5-((1H-pyrazol-4-yl)methylene)-2-thioxothiazolidin-4-one inhibitors of ADAMTS-5 (aggrecanase-2) is described. These compounds show microM functional inhibition of ADAMTS-5, and represent a new class of agents with the potential of inhibiting degradation of aggrecan, a major component of cartilage which is lost in osteoporosis. Compound 12 is noteworthy in that it has an ADAMTS-5 IC50: 1.1 microM and shows >40-fold functional selectivity over ADAMTS-4 (aggrecanase-1). 相似文献
163.
IL-6 and its soluble receptor augment aggrecanase-mediated proteoglycan catabolism in articular cartilage. 总被引:6,自引:0,他引:6
C R Flannery C B Little C E Hughes C L Curtis B Caterson S A Jones 《Matrix biology》2000,19(6):549-553
Elevated concentrations of interleukin-6 (IL-6) and soluble IL-6 receptor (sIL-6R) in the synovial fluids and serum of patients with arthritis have been implicated in the joint tissue destruction associated with these conditions, however studies conducted to date on the role and effects of IL-6 in the process of cartilage proteoglycan (aggrecan) catabolism are disparate. In the present study, bovine articular cartilage explants were maintained in a model organ culture system in the presence or absence of IL-1alpha or TNF-alpha, and under co-stimulation with or without IL-6 and/or sIL-6R. After measuring proteoglycan loss from the explants, the proteolytic activity and expression profiles of aggrecanase(s) was assessed for each culture condition. Stimulation of cartilage explants with IL-6 and/or sIL-6R potentiated aggrecan catabolism and release above that seen in the presence of IL-1alpha or TNF-alpha alone. This catabolism was associated with aggrecanase (but not MMP) activity, with correlative mRNA expression for aggrecanase-2. 相似文献
164.
G. P. Dowthwaite A. C. Ward J. Flannely R. F. L. Suswillo C. R. Flannery C. W. Archer A. A. Pitsillides 《Matrix biology》1999,18(6):749-532
The development of the synovial joint cavity between the cartilage anlagen of the long bones is thought to be mediated by differential matrix synthesis at the developing articular surfaces. In addition, many studies have shown that removal of movement-induced mechanical stimuli from developing diarthrodial joints prevents cavity formation or produces a secondary fusion of previously cavitated joints. Herein, we describe an inductive influence of mechanical strain on hyaluronan metabolism and the expression of hyaluronan-binding proteins in cultured cells isolated from the articular surface of the distal tibial condyles of 18-day chick embryos. The effect of 10 min of mechanical strain on hyaluronan release into culture media, intracellular uridine diphospho-glucose dehydrogenase activity (an enzyme required for hyaluronan saccharide precursor production), cell surface hyaluronan-binding protein expression and HA synthase mRNA expression were analysed up to 24 h later. Six hours after the application of strain, there was a significant increase in the accumulation of hyaluronan released into tissue culture media by strained fibrocartilage cells compared with controls, an effect still detectable after 24 h. Strained cells also showed increased activity for uridine diphospho-glucose dehydrogenase and expressed higher levels of the hyaluronan-binding protein CD44 at 24 h. In addition, at 24 h mRNA for HA synthase 2 was expressed in all samples whereas mRNA for HA synthase 3 was only expressed in strained cells. These results further highlight the role for movement-induced stimuli in differential extracellular matrix metabolism during joint development and also show that strain may facilitate differential HA synthase gene expression. 相似文献
165.
David M Markusic Niek P van Til Johan K Hiralall PJ Oude Ronald Elferink Jurgen Seppen 《BMC biotechnology》2009,9(1):85
Background
Lentiviral vectors are well suited for gene therapy because they can mediate long-term expression in both dividing and nondividing cells. However, lentiviral vectors seem less suitable for liver gene therapy because systemically administered lentiviral vectors are preferentially sequestered by liver macrophages. This results in a reduction of available virus and might also increase the immune response to the vector and vector products. 相似文献166.
Usurped SLRPs: novel arthritis biomarkers exposed by catabolism of small leucine-rich proteoglycans?
Flannery CR 《Arthritis research & therapy》2006,8(2):106-2
Proteolytic degradation of articular cartilage macromolecules, including the large aggregating cartilage proteoglycan (aggrecan)
and small leucine-rich proteoglycans (SLRPs), is a prominent pathophysiological feature of arthritic diseases such as osteoarthritis
(OA). Molecular profiling and monitoring of soluble/circulating proteoglycan catabolites that may be released from the cartilage
matrix therefore represents an attractive strategy for evaluating OA disease progression and intervention. The recent identification
of discrete metalloproteinase-sensitive SLRP cleavage sites, and complementary neoepitope-bearing SLRP catabolites, extends
decisive insight into the functional regulation of extracellular matrix integrity, and proffers poignant leads to assist in
disclosing and appraising applicable biomarkers of cartilage degeneration during arthritis. 相似文献
167.
Caitríona E. McInerney Joanna A. Lynn Alan R. Gilmore Tom Flannery Kevin M. Prise 《Current issues in molecular biology》2022,44(7):2982
Adult brain tumors (glioma) represent a cancer of unmet need where standard-of-care is non-curative; thus, new therapies are urgently needed. It is unclear whether isocitrate dehydrogenases (IDH1/2) when not mutated have any role in gliomagenesis or tumor growth. Nevertheless, IDH1 is overexpressed in glioblastoma (GBM), which could impact upon cellular metabolism and epigenetic reprogramming. This study characterizes IDH1 expression and associated genes and pathways. A novel biomarker discovery pipeline using artificial intelligence (evolutionary algorithms) was employed to analyze IDH-wildtype adult gliomas from the TCGA LGG-GBM cohort. Ninety genes whose expression correlated with IDH1 expression were identified from: (1) All gliomas, (2) primary GBM, and (3) recurrent GBM tumors. Genes were overrepresented in ubiquitin-mediated proteolysis, focal adhesion, mTOR signaling, and pyruvate metabolism pathways. Other non-enriched pathways included O-glycan biosynthesis, notch signaling, and signaling regulating stem cell pluripotency (PCGF3). Potential prognostic (TSPYL2, JAKMIP1, CIT, TMTC1) and two diagnostic (MINK1, PLEKHM3) biomarkers were downregulated in GBM. Their gene expression and methylation were negatively and positively correlated with IDH1 expression, respectively. Two diagnostic biomarkers (BZW1, RCF2) showed the opposite trend. Prognostic genes were not impacted by high frequencies of molecular alterations and only one (TMTC1) could be validated in another cohort. Genes with mechanistic links to IDH1 were involved in brain neuronal development, cell proliferation, cytokinesis, and O-mannosylation as well as tumor suppression and anaplerosis. Results highlight metabolic vulnerabilities and therapeutic targets for use in future clinical trials. 相似文献
168.
Background
Leucine-rich repeats are one of the more common modules found in proteins. The leucine-rich repeat consensus motif is LxxLxLxxNxLxxLxxLxxLxx- where the first 11–12 residues are highly conserved and the remainder of the repeat can vary in size Leucine-rich repeat proteins have been subdivided into seven subfamilies, none of which include members of the epidermal growth factor receptor or insulin receptor families despite the similarity between the 3D structure of the L domains of the type I insulin-like growth factor receptor and some leucine-rich repeat proteins. 相似文献169.
A Bell OA Rodríguez LA de Castro e Paula MB Padua J Hernández-Cerón CG Gutiérrez A De Vries PJ Hansen 《BMC veterinary research》2008,4(1):22
Background
Results regarding the use of bovine somatotropin for enhancing fertility in dairy cattle are variable. Here, the hypothesis was tested that a single injection of a sustained-release preparation of bovine somatotropin (bST) during the preovulatory period would improve pregnancy success of lactating dairy cows at first service.Results
The first experiment was conducted in a temperate region of Mexico. Cows inseminated following natural estrus or timed artificial insemination were given a single injection of bST or a placebo injection at insemination (n = 100 cows per group). There was no significant difference between bST and control groups in the proportion of inseminated cows diagnosed pregnant (29 vs 31% pregnant). The second experiment was performed during heat stress in Florida. Cows were subjected to an ovulation synchronization regimen for first insemination. Cows treated with bST received a single injection at 3 days before insemination. Controls received no additional treatment. As expected, bST did not increase vaginal temperature. Treatment with bST did not significantly increase the proportion of inseminated cows diagnosed pregnant although it was numerically greater for the bST group (24.2% vs 17.8%, 124–132 cows per group). There was a tendency (p = 0.10) for a smaller percent of control cows to have high plasma progesterone concentrations (≥ 1 ng/ml) at Day 7 after insemination than for bST-treated cows (72.6 vs 81.1%). When only cows that were successfully synchronized were considered, the magnitude of the absolute difference in the percentage of inseminated cows that were diagnosed pregnant between bST and control cows was reduced (24.8 vs 22.4% pregnant for bST and control).Conclusion
Results failed to indicate a beneficial effect of bST treatment on fertility of lactating dairy cows.170.
Jeffrey B. Olsen Penelope A. Crane Blair G. Flannery Karen Dunmall William D. Templin John K. Wenburg 《Conservation Genetics》2011,12(1):223-241
We examined the assumption that landscape heterogeneity similarly influences the spatial distribution of genetic diversity
in closely related and geographically overlapping species. Accordingly, we evaluated the influence of watershed affiliation
and nine habitat variables from four categories (spatial isolation, habitat size, climate, and ecology) on population divergence
in three species of Pacific salmon (Oncorhynchus tshawytscha, O. kisutch, and O. keta) from three contiguous watersheds in subarctic North America. By incorporating spatial data we found that the three watersheds
did not form the first level of hierarchical population structure as predicted. Instead, each species exhibited a broadly
similar spatial pattern: a single coastal group with populations from all watersheds and one or more inland groups primarily
in the largest watershed. These results imply that the spatial scale of conservation should extend across watersheds rather
than at the watershed level which is the scale for fishery management. Three independent methods of multivariate analysis
identified two variables as having influence on population divergence across all watersheds: precipitation in all species
and subbasin area (SBA) in Chinook. Although we found general broad-scale congruence in the spatial patterns of population
divergence and evidence that precipitation may influence population divergence in each species, we also found differences
in the level of population divergence (coho > Chinook and chum) and evidence that SBA may influence population divergence
only in Chinook. These differences among species support a species-specific approach to evaluating and planning for the influence
of broad-scale impacts such as climate change. 相似文献