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排序方式: 共有411条查询结果,搜索用时 187 毫秒
111.
Multiple points of interaction between retinoic acid and FGF signaling during embryonic axis formation 总被引:7,自引:0,他引:7
Shiotsugu J Katsuyama Y Arima K Baxter A Koide T Song J Chandraratna RA Blumberg B 《Development (Cambridge, England)》2004,131(11):2653-2667
Anteroposterior (AP) patterning of the developing CNS is crucial for both regional specification and the timing of neurogenesis. Several important factors are involved in AP patterning, including members of the WNT and FGF growth factor families, retinoic acid receptors, and HOX genes. We have examined the interactions between FGF and retinoic signaling pathways. Blockade of FGF signaling downregulates the expression of members of the RAR signaling pathway, RARalpha, RALDH2 and CYP26. Overexpression of a constitutively active RARalpha2 rescues the effects of FGF blockade on the expression of XCAD3 and HOXB9. This suggests that RARalpha2 is required as a downstream target of FGF signaling for the posterior expression of XCAD3 and HOXB9. Surprisingly, we found that posterior expression of FGFR1 and FGFR4 was dependent on the expression of RARalpha2. Anterior expression was also altered with FGFR1 expression being lost, whereas FGFR4 expression was expanded beyond its normal expression domain. RARalpha2 is required for the expression of XCAD3 and HOXB9, and for the ability of XCAD3 to induce HOXB9 expression. We conclude that RARalpha2 is required at multiple points in the posteriorization pathway, suggesting that correct AP neural patterning depends on a series of mutually interactive feedback loops among FGFs, RARs and HOX genes. 相似文献
112.
Inhibitory NK receptor Ly49Q is expressed on subsets of dendritic cells in a cellular maturation- and cytokine stimulation-dependent manner 总被引:5,自引:0,他引:5
Toyama-Sorimachi N Omatsu Y Onoda A Tsujimura Y Iyoda T Kikuchi-Maki A Sorimachi H Dohi T Taki S Inaba K Karasuyama H 《Journal of immunology (Baltimore, Md. : 1950)》2005,174(8):4621-4629
Ly49Q is a member of the Ly49 family that is expressed on Gr-1+ cells but not on NK and NKT cells. Ly49Q appears to be involved in regulating cytoskeletal architectures through ITIM-mediated signaling. We provide evidence that dendritic cells (DCs) of certain maturational states expressed Ly49Q, and that IFN-alpha plays an important role in its regulation. Freshly prepared murine plasmacytoid pre-DCs as well as Flt3L-induced plasmacytoid pre-DCs expressed Ly49Q, whereas freshly prepared myeloid DCs did not. However, GM-CSF-induced myeloid DCs showed low levels of Ly49Q expression, and this was significantly enhanced by IFN-alpha. In contrast, other cytokines and ligands for TLRs such as TNF-alpha, IL-6, LPS, and CpG-ODN had little or no effect on Ly49Q expression. Plasmacytoid pre-DCs in all mouse strains examined expressed Ly49Q. Constitutive expression of Ly49Q on myeloid DCs was observed in three restricted mouse strains including 129, NZB, and NZW. As can be seen in other Ly49 family members, Ly49Q expression was affected by MHC class I expression. At the same time, Ly49Q possessed polymorphisms, including at least three alleles. The polymorphic residues lay within the stalk and carbohydrate recognition domain, and two of them, in loop 3 and loop 6 of the carbohydrate recognition domain, are located in the region implicated in the interaction of Ly49A with H-2D(d). Therefore, depending on IFN-alpha, our results imply that Ly49Q serves a role for the biological functions of certain DC subsets through recognition of MHC class I or related molecules. 相似文献
113.
Vitellogenin (VTG) produced in male fish has been used for a biomarker to study endocrine disrupters. However, the characteristics of VTG produced in male fish have not been studied well. In this study, we investigated the localization of VTG in the liver and the testis of male medaka (Oryzias latipes) treated with 17beta-estradiol (E2) and p-nonylphenol (NP). The male fish were exposed to 1 microg/L E2 and 500 microg/L NP for 1-12 days. Control groups were kept in water including only vehicle. The frozen sections of the liver and the testis were stained with immunohistochemical methods using an antiserum against medaka VTG as the first antibody. In the E2 and NP treated liver, the hepatocytes showed immunoreactivity. In particular, the cytoplasm close to the cell membrane surrounding the sinusoids was strongly immunopositive. In the testis of both treatments, the interstitial tissues and the cells (spermatocytes) in the seminiferous tubules were immunopositive. The concentration of VTG became gradually higher in both tissues with longer treatments. These results suggest that germ cells in the testis treated with E2 and NP are able to incorporate and accumulate VTG. 相似文献
114.
Edwards JW Page GP Gadbury G Heo M Kayo T Weindruch R Allison DB 《Functional & integrative genomics》2005,5(1):32-39
Micro-array technology allows investigators the opportunity to measure expression levels of thousands of genes simultaneously. However, investigators are also faced with the challenge of simultaneous estimation of gene expression differences for thousands of genes with very small sample sizes. Traditional estimators of differences between treatment means (ordinary least squares estimators or OLS) are not the best estimators if interest is in estimation of gene expression differences for an ensemble of genes. In the case that gene expression differences are regarded as exchangeable samples from a common population, estimators are available that result in much smaller average mean-square error across the population of gene expression difference estimates. We have simulated the application of such an estimator, namely an empirical Bayes (EB) estimator of random effects in a hierarchical linear model (normal-normal). Simulation results revealed mean-square error as low as 0.05 times the mean-square error of OLS estimators (i.e., the difference between treatment means). We applied the analysis to an example dataset as a demonstration of the shrinkage of EB estimators and of the reduction in mean-square error, i.e., increase in precision, associated with EB estimators in this analysis. The method described here is available in software that is available at . 相似文献
115.
Li Y Kataoka M Tatsuta M Yasoshima K Yura T Urbahns K Kiba A Yamamoto N Gupta JB Hashimoto K 《Bioorganic & medicinal chemistry letters》2005,15(3):805-807
The 2-cyclopropyl substituted benzimidazole 2 has been used as a starting point for further optimization of an LHRH antagonist series. SAR studies revealed that a tert-butyl urea fragment connected through a simple carbon chain would improve activity. Further modification of the benzylsulfonamide moiety led to the discovery of 23 (IC(50): 4.2 nM). 相似文献
116.
Yudoh K Nguyen vT Nakamura H Hongo-Masuko K Kato T Nishioka K 《Arthritis research & therapy》2005,7(2):R380-R391
Oxidative stress leads to increased risk for osteoarthritis (OA) but the precise mechanism remains unclear. We undertook this
study to clarify the impact of oxidative stress on the progression of OA from the viewpoint of oxygen free radical induced
genomic instability, including telomere instability and resulting replicative senescence and dysfunction in human chondrocytes.
Human chondrocytes and articular cartilage explants were isolated from knee joints of patients undergoing arthroplastic knee
surgery for OA. Oxidative damage and antioxidative capacity in OA cartilage were investigated in donor-matched pairs of intact
and degenerated regions of tissue isolated from the same cartilage explants. The results were histologically confirmed by
immunohistochemistry for nitrotyrosine, which is considered to be a maker of oxidative damage. Under treatment with reactive
oxygen species (ROS; 0.1 μmol/l H2O2) or an antioxidative agent (ascorbic acid: 100.0 μmol/l), cellular replicative potential, telomere instability and production
of glycosaminoglycan (GAG) were assessed in cultured chondrocytes. In tissue cultures of articular cartilage explants, the
presence of oxidative damage, chondrocyte telomere length and loss of GAG to the medium were analyzed in the presence or absence
of ROS or ascorbic acid. Lower antioxidative capacity and stronger staining of nitrotyrosine were observed in the degenerating
regions of OA cartilages as compared with the intact regions from same explants. Immunostaining for nitrotyrosine correlated
with the severity of histological changes to OA cartilage, suggesting a correlation between oxidative damage and articular
cartilage degeneration. During continuous culture of chondrocytes, telomere length, replicative capacity and GAG production
were decreased by treatment with ROS. In contrast, treatment with an antioxidative agent resulted in a tendency to elongate
telomere length and replicative lifespan in cultured chondrocytes. In tissue cultures of cartilage explants, nitrotyrosine
staining, chondrocyte telomere length and GAG remaining in the cartilage tissue were lower in ROS-treated cartilages than
in control groups, whereas the antioxidative agent treated group exhibited a tendency to maintain the chondrocyte telomere
length and proteoglycan remaining in the cartilage explants, suggesting that oxidative stress induces chondrocyte telomere
instability and catabolic changes in cartilage matrix structure and composition. Our findings clearly show that the presence
of oxidative stress induces telomere genomic instability, replicative senescence and dysfunction of chondrocytes in OA cartilage,
suggesting that oxidative stress, leading to chondrocyte senescence and cartilage ageing, might be responsible for the development
of OA. New efforts to prevent the development and progression of OA may include strategies and interventions aimed at reducing
oxidative damage in articular cartilage. 相似文献
117.
Yuriko Uehara Katsutoshi Oda Yuji Ikeda Takahiro Koso Shingo Tsuji Shogo Yamamoto Kayo Asada Kenbun Sone Reiko Kurikawa Chinami Makii Otoe Hagiwara Michihiro Tanikawa Daichi Maeda Kosei Hasegawa Shunsuke Nakagawa Osamu Wada-Hiraike Kei Kawana Masashi Fukayama Keiichi Fujiwara Tetsu Yano Yutaka Osuga Tomoyuki Fujii Hiroyuki Aburatani 《PloS one》2015,10(7)
118.
Naoyoshi Nagata Kayo Sakamoto Tomohiro Arai Ryota Niikura Takuro Shimbo Masafumi Shinozaki Noriko Ihana Katsunori Sekine Hidetaka Okubo Kazuhiro Watanabe Toshiyuki Sakurai Chizu Yokoi Mikio Yanase Junichi Akiyama Naomi Uemura Mitsuhiko Noda 《PloS one》2015,10(4)
Background
This study aims to investigate the association between body mass index (BMI) or intra-abdominal fat measured by computed tomography (CT) and bowel symptoms.Method
A cohort of 958 Japanese adults who underwent colonoscopy and CT and completed questionnaires after excluding colorectal diseases was analyzed. Six symptoms (constipation, diarrhea, loose stools, hard stools, fecal urgency, and incomplete evacuation) using a 7-point Likert scale were evaluated between baseline and second questionnaire for test-retest reliability. Associations between BMI, visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and symptom score were analyzed by a rank-ordered logistic model, adjusting for age, sex, smoking, and alcohol consumption, hypertension, diabetes mellitus, and dyslipidemia.Results
Some bowel symptom scores were significantly (p<0.05) different between the age groups, sexes, smoking, and alcohol consumption. In multivariate analysis, constipation was associated with low BMI (p<0.01), low VAT area (p = 0.01), and low SAT area (p<0.01). Moreover, hard stools was associated with low BMI (p<0.01) and low SAT area (p<0.01). The remaining symptoms were not significantly associated with BMI or intra-abdominal fat. Test-retest reliability of bowel symptom scores with a mean duration of 7.5 months was good (mean kappa, 0.672).Conclusions
Both low BMI and low abdominal fat accumulation appears to be useful indicators of increased risk for constipation and hard stools. The long-term test-retest reliability of symptom score suggests that bowel symptoms relevant to BMI or visceral fat remain consistent over several months. 相似文献119.
120.