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91.
Kim YG Ohta T Takahashi T Kushiro A Nomoto K Yokokura T Okada N Danbara H 《Microbes and infection / Institut Pasteur》2006,8(4):994-1005
Probiotic bacteria are microorganisms that benefit the host through improvement of the balance of intestinal microflora and possibly by augmentation of host defense systems. We examined the mechanisms for the up-regulation of innate immune responses by a probiotic Lactobacillus casei ATCC27139, in vivo. Using mouse models of systemic Listeria monocytogenes infection and MethA fibrosarcoma tumorigenesis in combination with BALB/c and SCID mice, we found that parenteral administration of L. casei ATCC27139 confers a protective effect against L. monocytogenes infection and anti-tumor activity against MethA fibrosarcoma by activation of innate immunity, while L. casei ATCC27139-J1R strains, which are J1 phage-resistant strains that have been selected from MNNG-treated clones, lacked these activities. Substantial differences between ATCC27139 and ATCC27139-J1R strains were observed in the capacity to induce innate cytokines such as TNF-alpha, IL-12, IL-18, and IFN-gamma, and pathogen-associated molecular pattern receptors, TLR2 and Nod2, by spleen cells. In addition, although phosphorylation of NF-kappaB p65 in spleen was equally enhanced in the ATCC27139- and the ATCC27139-J1R-treated groups, phosphorylation of both p38 MAPK and MAPKAPK-2 was significantly induced only by ATCC27139. Furthermore, inhibitors of NF-kappaB (sulfasalazine) and p38 MAPK (SB203580) significantly reduced cytokine production by the spleen cells of the mice treated with L. casei ATCC27139, suggesting that both NF-kappaB and p38 MAPK signaling pathways play important roles in the augmentation of innate immunity by the probiotic L. casei. 相似文献
92.
Shobayashi M Mukai N Iwashita K Hiraga Y Iefuji H 《Applied microbiology and biotechnology》2006,69(6):704-710
S-Adenosylmethionine (SAM) is an important metabolite that participates in many reactions as a methyl group donor in all organisms,
and has attracted much interest in clinical research because of its potential to improve many diseases, such as depression,
liver disease, and osteoarthritis. Because of these potential applications, a more efficient means is needed to produce SAM.
Accordingly, we developed a positive selection method to isolate SAM-accumulating yeast in this study. In Saccharomyces cerevisiae, one of the main reactions consuming SAM is thought to be the methylation reaction in the biosynthesis of ergosterol that
is catalyzed by Erg6p. Mutants with deficiencies in ergosterol biosynthesis may accumulate SAM as a result of the reduction
of SAM consumption in ergosterol biosynthesis. We have applied this method to isolate SAM-accumulating yeasts with nystatin,
which has been used to select mutants with deficiencies in ergosterol biosynthesis. SAM-accumulating mutants from S. cerevisiae K-9 and X2180-1A were efficiently isolated through this method. These mutants accumulated 1.7–5.5 times more SAM than their
parental strains. NMR and GC-MS analyses suggested that two mutants from K-9 have a mutation in the erg4 gene, and erg4 disruptants from laboratory strains also accumulated more SAM than their parental strains. These results indicate that mutants
having mutations in the genes for enzymes that act downstream of Erg6p in ergosterol biosynthesis are effective in accumulating
SAM. 相似文献
93.
Maturation of circulating dendritic cells and imbalance of T-cell subsets in patients with squamous cell carcinoma of the head and neck 总被引:5,自引:0,他引:5
Sakakura K Chikamatsu K Takahashi K Whiteside TL Furuya N 《Cancer immunology, immunotherapy : CII》2006,55(2):151-159
Interactions between dendritic cells (DCs) and T cells play a pivotal role in the regulation and maintenance of immune responses.
In cancer patients, various immunological abnormalities have been observed in these immune cells. Here, we investigated proportions
and the phenotype of DCs and the cytokine profile of T-cell subsets in the peripheral blood of patients with squamous cell
carcinoma of the head and neck (SCCHN), using multicolor flow cytometry. The percentage of myeloid (CD11c+), but not plasmacytoid
(CD123+) DCs, was significantly lower (P<0.05) and expression of HLA-DR was significantly decreased in total and myeloid DCs of cancer patients compared to healthy
donors. Simultaneous analyses of T-cell subsets in the patients’ circulation showed significantly increased proportions of
CD4+ T cells expressing Th1 and Th2 cytokines after ex vivo stimulation without any skewing in the Th1/Th2 ratio. The relative
level of HLA-DR expression on myeloid or total DCs positively correlated with the Th1/Th2 ratio (P<0.01), and the proportion of total circulating DCs was inversely correlated with that of regulatory CD4+CD25+ T cells (P<0.01). These results suggest that the decreased proportion of circulating DCs and decreased HLA-DR expression in DCs may
have a major impact on systemic immune responses in patients with SCCHN. 相似文献
94.
Sakabe E Tanaka N Shimozono N Gojobori T Fujiwara S 《Development, growth & differentiation》2006,48(6):391-400
Fibroblast growth factor (FGF) induces the notochord and mesenchyme in ascidian embryos, via extracellular signal-regulated kinase (ERK) that belongs to the mitogen-activated protein kinase (MAPK) family. A cDNA microarray analysis was carried out to identify genes affected by an inhibitor of MAPK/ERK kinase (MEK), U0126, in embryos of the ascidian Ciona intestinalis. Data obtained from the microarray and in situ hybridization suggest that the majority of genes are downregulated by U0126 treatment. Genes that were downregulated in U0126-treated embryos included Ci-Bra and Ci-Twist-like1 that are master regulatory genes of notochord and mesenchyme differentiation, respectively. The plasminogen mRNA was downregulated by U0126 in presumptive endoderm cells. This suggests that a MEK-mediated extracellular signal is necessary for gene expression in tissues whose specification does not depend on cell-to-cell interaction. Among 85 cDNA clusters that were not affected by U0126, 30 showed mitochondria-like mRNA localization in the nerve cord/muscle lineage blastomeres in the equatorial region. The expression level and asymmetric distribution of these mRNA were independent of MEK signaling. 相似文献
95.
Mortality of mouse keratinocytes Pam212 that were irradiated with ultraviolet-B (UVB) was shown to be repressed by pre-irradiated administration with L-ascorbic acid (Asc) or more markedly with Asc-2-O-phosphate (Asc2P), but not with dehydroascorbic acid (DehAsc) or Asc-2-O-alpha-glucoside (Asc2G), although not repressed by post-irradiated administration. The cytoprotection by Asc2P was restricted against UVB below 5-20 mJ/cm2, and exhibited markedly by administration for a period over 2 h, which may be caused by intracellular Asc that was accumulated via dephosphorylation of Asc2P and was increased, 6-24 h after, to levels above twice as abundant as those of Asc-administration. Pre-irradiated Asc2P-administration slightly repressed a DNA ladder-like electrophoretic pattern for UVB-irradiated keratinocytes, containing the histone-bound DNA fragments as shown by ELISA assay, and appreciably repressed the DNA-3'OH cleavage terminals as shown by terminal deoxyribonucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) stain. Thus, prevention of UVB-induced cell death by Asc2P was shown to occur concurrently with inhibition of DNA cleavages and enrichment of intracellular Asc. 相似文献
96.
Saitoh Y Mizuno H Xiao L Hyoudou S Kokubo K Miwa N 《Molecular and cellular biochemistry》2012,366(1-2):191-200
Reactive oxygen species has been suggested to be one of the key factors associated with the development of obesity. During spontaneous differentiation of mouse stromal preadipocytes OP9 into adipocytes, intracellular superoxide anion radicals (O (2) (-.) ) level markedly increases and is accompanied by a significant elevation of intracellular lipid accumulation. This differentiation-dependent increase in intracellular O (2) (-.) level positively correlated with the intracellular augmentation of the lipid level. Super-highly hydroxylated fullerene (SHH-F; C(60)(OH)(44)), a novel polyhydroxylated fullerene derivative, quenched intracellular O (2) (-.) , and lipid accumulation to 38.7 and 42.7 % of that in the control, respectively. By thin-layer chromatographic analysis of extracted cellular lipid components, SHH-F clearly decreased the triglycerides ratio in the whole lipid droplet fraction, but scarcely influenced other lipids components. PPARγ2 expression, which plays a key role in regulating adipogenic differentiation, was significantly suppressed by SHH-F at the late stage of differentiation, with unaltered PPARγ1 expression. The intracellular superoxide anion radical augmentation preceded expression of PPARγ2, strongly suggesting that the primary O (2) (-.) generation was closely associated with lipid accumulation and subsequent PPARγ2 induction. These results indicate that SHH-F suppresses intracellular lipid accumulation, particularly in lipid droplets, and decreases O (2) (-.) level and subsequent PPARγ2 upregulation during spontaneous differentiation of OP9 preadipocytes into adipocytes. 相似文献
97.
Light microscopic imaging of blood vessels and distribution of serum proteins is essential to analyze hemodynamics in living
animal lungs under normal respiration or respiratory diseases. In this study, to demonstrate dynamically changing morphology
and immunohistochemical images of their living states, “in vivo cryotechnique” (IVCT) combined with freeze-substitution fixation
was applied to anesthetized mouse lungs. By hematoxylin–eosin staining, morphological features, such as shapes of alveolar
septum and sizes of alveolar lumen, reflected their respiratory conditions in vivo, and alveolar capillaries were filled with
variously shaped erythrocytes. Albumin was usually immunolocalized in the capillaries, which was confirmed by double-immunostaining
for aquaporin-1 of endothelium. To capture accurate time-courses of blood flow in peripheral pulmonary alveoli, glutathione-coated
quantum dots (QDs) were injected into right ventricles, and then IVCT was performed at different time-points after the QD
injection. QDs were localized in most arterioles and some alveolar capillaries at 1 s, and later in venules at 2 s, reflecting
a typical blood flow direction in vivo. Three-dimensional QD images of microvascular networks were reconstructed by confocal
laser scanning microscopy. It was also applied to lungs of acute pulmonary hypertension mouse model. Erythrocytes were crammed
in blood vessels, and some serum components leaked into alveolar lumens, as confirmed by mouse albumin immunostaining. Some
separated collagen fibers and connecting elastic fibers were still detected in edematous tunica adventitia near terminal bronchioles.
Thus, IVCT combined with histochemical approaches enabled us to capture native images of dynamically changing structures and
microvascular hemodynamics of living mouse lungs. 相似文献
98.
ABSTRACT: BACKGROUND: Striae gravidarum is a physiological skin change that many pregnant women experience during pregnancy. The striae are often accompanied by a reddish purple color during pregnancy, and then lose pigmentation and become atrophic in the long term after pregnancy. Striae gravidarum seems to be undesirable to many pregnant women. However, the impact of striae gravidarum on pregnant women who experience it has not been clarified. The aim of this study was to evaluate the impact of striae gravidarum on the generic and dermatology-specific quality of life (QOL) of pregnant women. METHODS: A cross-sectional study was conducted at three private clinics in a typical urban area in Japan. We recruited 447 pregnant women at 36 weeks of gestation; One hundred and ninety-nine pregnant women at 36 weeks of gestation participated in the study and 179, consisting of 94 primiparae and 85 multiparae, were analyzed.We used and assessed Davey's score for striae gravidarum, World Health Organization Quality of Life assessment questionnaire for generic QOL, and Skindex-29 for dermatology-specific QOL. RESULTS: The prevalence of striae gravidarum was 39.1% (27.7% in primiparae, and 51.8% in multiparae). Although there were no differences in generic QOL scores between the presence and absence of striae gravidarum and with their severity, the whole group of pregnant women and the multiparae group showed significant differences in scores on emotion of Skindex-29 between the presence and absence of striae gravidarum (p = 0.012 and p = 0.011). Pregnant women with severe striae gravidarum showed significantly higher scores on emotion of Skindex-29 compared with those with absent or mild striae gravidarum (p < 0.001 and p = 0.005). CONCLUSIONS: There was no difference in generic QOL of pregnant women between the presence and absence of striae gravidarum, although the occurrence and severity of striae gravidarum influenced their dermatology-specific QOL. Multiparae women were especially impaired by striae gravidarum and it is considered important to prevent or reduce the severity of striae gravidarum of the multiparae group. 相似文献
99.
Cantrup R Dixit R Palmesino E Bonfield S Shaker T Tachibana N Zinyk D Dalesman S Yamakawa K Stell WK Wong RO Reese BE Kania A Sauvé Y Schuurmans C 《PloS one》2012,7(3):e32795
Background
The retina has a unique three-dimensional architecture, the precise organization of which allows for complete sampling of the visual field. Along the radial or apicobasal axis, retinal neurons and their dendritic and axonal arbors are segregated into layers, while perpendicular to this axis, in the tangential plane, four of the six neuronal types form patterned cellular arrays, or mosaics. Currently, the molecular cues that control retinal cell positioning are not well-understood, especially those that operate in the tangential plane. Here we investigated the role of the PTEN phosphatase in establishing a functional retinal architecture.Methodology/Principal Findings
In the developing retina, PTEN was localized preferentially to ganglion, amacrine and horizontal cells, whose somata are distributed in mosaic patterns in the tangential plane. Generation of a retina-specific Pten knock-out resulted in retinal ganglion, amacrine and horizontal cell hypertrophy, and expansion of the inner plexiform layer. The spacing of Pten mutant mosaic populations was also aberrant, as were the arborization and fasciculation patterns of their processes, displaying cell type-specific defects in the radial and tangential dimensions. Irregular oscillatory potentials were also observed in Pten mutant electroretinograms, indicative of asynchronous amacrine cell firing. Furthermore, while Pten mutant RGC axons targeted appropriate brain regions, optokinetic spatial acuity was reduced in Pten mutant animals. Finally, while some features of the Pten mutant retina appeared similar to those reported in Dscam-mutant mice, PTEN expression and activity were normal in the absence of Dscam.Conclusions/Significance
We conclude that Pten regulates somal positioning and neurite arborization patterns of a subset of retinal cells that form mosaics, likely functioning independently of Dscam, at least during the embryonic period. Our findings thus reveal an unexpected level of cellular specificity for the multi-purpose phosphatase, and identify Pten as an integral component of a novel cell positioning pathway in the retina. 相似文献100.