全文获取类型
收费全文 | 542篇 |
免费 | 24篇 |
国内免费 | 1篇 |
专业分类
567篇 |
出版年
2022年 | 5篇 |
2021年 | 12篇 |
2020年 | 3篇 |
2019年 | 8篇 |
2018年 | 4篇 |
2017年 | 13篇 |
2016年 | 19篇 |
2015年 | 18篇 |
2014年 | 28篇 |
2013年 | 33篇 |
2012年 | 37篇 |
2011年 | 36篇 |
2010年 | 16篇 |
2009年 | 32篇 |
2008年 | 43篇 |
2007年 | 34篇 |
2006年 | 26篇 |
2005年 | 42篇 |
2004年 | 38篇 |
2003年 | 22篇 |
2002年 | 23篇 |
2001年 | 6篇 |
2000年 | 7篇 |
1999年 | 7篇 |
1998年 | 3篇 |
1997年 | 6篇 |
1996年 | 7篇 |
1995年 | 2篇 |
1994年 | 1篇 |
1993年 | 5篇 |
1992年 | 2篇 |
1991年 | 1篇 |
1990年 | 5篇 |
1989年 | 3篇 |
1988年 | 2篇 |
1987年 | 3篇 |
1985年 | 2篇 |
1984年 | 1篇 |
1983年 | 1篇 |
1982年 | 5篇 |
1981年 | 1篇 |
1980年 | 2篇 |
1979年 | 1篇 |
1977年 | 1篇 |
1970年 | 1篇 |
排序方式: 共有567条查询结果,搜索用时 15 毫秒
41.
Naoto Takahashi Hisaya Hasegawa Mami Komiyama Takehiro Ohki Yukari Yada Yasunori Koike Ryou Kawamata Yoko Honma Mariko Momoi 《Cytokine》2009,45(1):39-43
Neonatal toxic shock syndrome (TSS)-like exanthematous disease (NTED) is an emerging neonatal infectious disease caused by TSS toxin-1 (TSST-1). Although NTED and TSS are caused by the same superantigenic exotoxin, NTED is less severe than TSS. The mechanism of this reduced severity in NTED has not been elucidated. Thirteen patients with NTED were enrolled in the study. We investigated serum cytokine profile using a cytometric bead array system with a cytokine panel. Expression of Vβ2 and CD45RO in CD4+ T cells was investigated in mononuclear cells by using flowcytometry. Ten patients with other bacterial infections and eight patients without any infections were also enrolled as control groups. The mean serum level of IL-10 was 1209.9 pg/mL in patients with NTED at the time of admission into the study. The other inhibitory cytokine, IL-4, exhibited a minimum level. The high level of IL-10 rapidly decreased within 3–9 days of the onset of NTED. The cytokine profile of NTED, with its high IL-10 level, was clearly different from that of the other bacterial infections. The increased level of IL-10 seems to be related to the reduced severity of NTED. Th2 shift is not thought to be the cause of this IL-10 excretion. 相似文献
42.
Naoya Yoshihara Taiji Sakamoto Takehiro Yamashita Toshifumi Yamashita Keita Yamakiri Shozo Sonoda Tatsuro Ishibashi 《PloS one》2015,10(4)
Purpose
To determine whether the width of the retinal artery (RA) trajectory was associated with the presence of a macular hole (MH).Methods
A retrospective cross sectional case-control study was performed. The fundus photographs were rotated 90 degrees, and the coordinates of the best fit curve of the RA trajectory were determined automatically based on these plots using the ImageJ program. The converted coordinates were fit to a second degree polynomial (ax2/100 + bx + c) equation. The width and steepness of the RA trajectory, “a”, of the eyes with a MH eye were compared to that of the fellow eyes.Results
One hundred and ten eyes of 55 consecutive patients (30 women) with a unilateral MH and healthy fellow eyes were analyzed. The mean age was 64.9 years (range 47-81 years). The constant ‘a’ was significantly smaller in eyes with a MH than that of the fellow eyes (0.379 ± 0.094 vs 0.416 ± 0.121, P = 0.001, paired t test), indicating that the RA trajectory was wider in the MH eyes than in the fellow eyes. There was a significant correlation between the axial length and ‘a’ of the RA trajectory in the MH eyes (R = 0.273, P = 0.044) and in the fellow eyes (R = 0.356, P = 0.008; Spearman’s rank correlation coefficient).Conclusions
Because eyes with a MH have a significantly wider and flatter RA trajectory, there may be greater traction on the fovea which is located between the RA arches. The causative role of this finding is still unclear. 相似文献43.
Mineo Kondo Gautami Das Ryoetsu Imai Evelyn Santana Tomio Nakashita Miho Imawaka Kosuke Ueda Hirohiko Ohtsuka Kazuhiko Sakai Takehiro Aihara Kumiko Kato Masahiko Sugimoto Shinji Ueno Yuji Nishizawa Gustavo D. Aguirre Keiko Miyadera 《PloS one》2015,10(9)
Congenital stationary night blindness (CSNB) is a non-progressive, clinically and genetically heterogeneous disease of impaired night vision. We report a naturally-occurring, stationary, autosomal recessive phenotype in beagle dogs with normal daylight vision but absent night vision. Affected dogs had normal retinas on clinical examination, but showed no detectable rod responses. They had “negative-type” mixed rod and cone responses in full-field ERGs. Their photopic long-flash ERGs had normal OFF-responses associated with severely reduced ON-responses. The phenotype is similar to the Schubert-Bornschein form of complete CSNB in humans. Homozygosity mapping ruled out most known CSNB candidates as well as CACNA2D4 and GNB3. Three remaining genes were excluded based on sequencing the open reading frame and intron-exon boundaries (RHO, NYX), causal to a different form of CSNB (RHO) or X-chromosome (NYX, CACNA1F) location. Among the genes expressed in the photoreceptors and their synaptic terminals, and mGluR6 cascade and modulators, reduced expression of GNAT1, CACNA2D4 and NYX was observed by qRT-PCR in both carrier (n = 2) and affected (n = 2) retinas whereas CACNA1F was down-regulated only in the affecteds. Retinal morphology revealed normal cellular layers and structure, and electron microscopy showed normal rod spherules and synaptic ribbons. No difference from normal was observed by immunohistochemistry (IHC) for antibodies labeling rods, cones and their presynaptic terminals. None of the retinas showed any sign of stress. Selected proteins of mGluR6 cascade and its modulators were examined by IHC and showed that PKCα weakly labeled the rod bipolar somata in the affected, but intensely labeled axonal terminals that appeared thickened and irregular. Dendritic terminals of ON-bipolar cells showed increased Goα labeling. Both PKCα and Goα labeled the more prominent bipolar dendrites that extended into the OPL in affected but not normal retinas. Interestingly, RGS11 showed no labeling in the affected retina. Our results indicate involvement of a yet unknown gene in this canine model of complete CSNB. 相似文献
44.
Hanae Takatsuki Katsuya Satoh Kazunori Sano Takayuki Fuse Takehiro Nakagaki Tsuyoshi Mori Daisuke Ishibashi Ban Mihara Masaki Takao Yasushi Iwasaki Mari Yoshida Ryuichiro Atarashi Noriyuki Nishida 《PloS one》2015,10(6)
The infectious agents of the transmissible spongiform encephalopathies are composed of amyloidogenic prion protein, PrPSc. Real-time quaking-induced conversion can amplify very small amounts of PrPSc seeds in tissues/body fluids of patients or animals. Using this in vitro PrP-amyloid amplification assay, we quantitated the seeding activity of affected human brains. End-point assay using serially diluted brain homogenates of sporadic Creutzfeldt–Jakob disease patients demonstrated that 50% seeding dose (SD50) is reached approximately 1010/g brain (values varies 108.79–10.63/g). A genetic case (GSS-P102L) yielded a similar level of seeding activity in an autopsy brain sample. The range of PrPSc concentrations in the samples, determined by dot-blot assay, was 0.6–5.4 μg/g brain; therefore, we estimated that 1 SD50 unit was equivalent to 0.06–0.27 fg of PrPSc. The SD50 values of the affected brains dropped more than three orders of magnitude after autoclaving at 121°C. This new method for quantitation of human prion activity provides a new way to reduce the risk of iatrogenic prion transmission. 相似文献
45.
Takehiro Sasaki Yu Yoshihara Undarmaa Jamsran Toshiya Ohkuro 《Ecological Engineering》2010,36(8):1070-1075
Plant facilitation (positive plant–plant interactions) strongly influences biodiversity, structure, and dynamics in plant communities, and the topic has received considerable attention among ecologists. Most studies of facilitation processes by shrubs have been conducted at small spatial scales between shrubs and their neighboring species. Yet, we know little about whether facilitation processes by shrubs at a small scale (i.e., a patch scale) also work at a larger scale (i.e., a site scale) in terms of the maintenance of biodiversity. Here, we report that the facilitative effects of shrubs on plant diversity at a larger scale can be explained by changing ecological stoichiometry. The soil fertility showed unimodal shape along shrub cover gradient, suggesting that the facilitative effects of a shrub do not necessarily increase as the shrub develops. The unimodal shape of dependence of plant species richness on shrub cover probably was generated by the unimodal dependence of soil fertility on shrub cover. Soil nutrient enrichment by shrubs shifted low N:P ratios of plant communities with low levels of shrub cover to more balanced N:P ratios at intermediate levels of shrub cover. At the peak N:P ratio along the gradient in shrub cover, the maximum species richness and functional richness were observed, which was consistent with the unimodal relationship predicted by the resource balance hypothesis. Thus, our findings showed that facilitation processes by shrubs at a patch scale also work at a larger scale in terms of the maintenance of biodiversity. Because observed larger-scale facilitation processes are enhanced at some intermediate levels of shrub cover, this study offers practical insight into the need for management practices that allow some intermediate levels of grazing by livestock for optimizing the role of larger-scale facilitation processes in the maintenance of biodiversity and ecosystem functioning in arid and semi-arid rangelands. 相似文献
46.
Yu Yoshihara Takehiro Sasaki Toshiya Okuro Jamsran Undarmaa Kazuhiko Takeuchi 《Ecological Engineering》2010,36(12):1719-1724
Facilitation (positive plant–plant interactions) is a potential means to accelerate vegetation restoration in arid areas. Shrubs can accelerate vegetation recovery by means of soil amelioration, but this effect has not been evaluated at large spatial scales or across scales. Here, we examined the facilitative function of shrub change across spatial scales at a desert steppe in Mongolia. Using a high-resolution satellite image, we established five 2500 m2 plots in each of three shrub density classes (low, moderate, high) in a desert steppe in Mongolia. To evaluate the facilitative functions of shrubs at multiple spatial scales, we recorded the total number of plant species at three nested spatial scales in each plot: 25, 400, and 2500 m2. The facilitative effect of shrubs on plant species richness was more pronounced at larger scales. Denser shrub communities increased plant species diversity at a larger scale. However, the increased taxonomic diversity was not clearly related to increased functional diversity in this system. This scale dependency in species diversity can be explained by the degree to which spatial heterogeneity of habitats within the plots increased as plot size increased. These results support the hypothesis of scale-dependent changes in the balance between facilitation and competition. Therefore, transplanting shrub saplings at high-density and a larger scale could potentially improve the success of vegetation restoration in arid regions. 相似文献
47.
Ca2+-signaling in downstream effectors is supported by many kinds of Ca2+-binding proteins, which function as a signal mediator and a Ca2+-buffering protein. We found in Arabidopsis thaliana a new type of Ca2+-binding protein, CCaP1, which consists of 152 amino acid residues, and binds (45)Ca2+ even in the presence of a high concentration of Mg2+. We found two other proteins with similar motifs, CCaP2 and CCaP3. These three proteins had no organelle localization signal and their green fluorescent protein (GFP) fusions were detected in the cytosol. Real-time PCR and histochemical analysis of promoter-beta-glucuronidase fusions revealed that CCaP1 was predominantly expressed in petioles while CCaP2 was expressed in roots. CCaP3 was hardly expressed. Expression of CCaP1 and CCaP2 was enhanced in darkness and became maximal after 24 h. Immunoblotting revealed petiole-specific accumulation of CCaP1. Expression of CCaP1 and CCaP2 was suppressed by a high concentration of Ca2+ and other metal ions. Deletion of sucrose from the medium markedly increased the mRNA levels of CCaP1 and CCaP2 within 2 h. Gibberellic acid enhanced the expression of CCaP1 and CCaP2 by 5- and 2.5-fold, respectively, after 6 h. CCaP1 and CCaP2 were suppressed in the petiole and the root, respectively, by light and the product of photosynthesis (sucrose) or both. These results suggest that CCaP1 functions as a mediator in response to continuous dark or gibberellic acid. 相似文献
48.
Gao SY Li CY Shimokawa T Terashita T Matsuda S Yaoita E Kobayashi N 《Cell and tissue research》2007,328(2):391-400
Intercellular adhesions between renal glomerular epithelial cells (also called podocytes) are necessary for the proper function
of the glomerular filtration barrier. Although our knowledge of the molecular composition of podocyte cell-cell contact sites
has greatly progressed, the underlying molecular mechanism regulating the formation of these cell-cell contacts remains largely
unknown. We have used forskolin, an activator of adenylyl cyclase that elevates the level of intracellular cAMP, to investigate
the effect of cAMP and three Rho-family small GTPases (RhoA, Cdc42, and Rac1) on the regulation of cell-cell contact formation
in a murine podocyte cell line. Transmission electron microscopy and the immunostaining of cell adhesion molecules and actin-associated
proteins have revealed a structural change at the site of cell-cell contact following forskolin treatment. The activity of
the Rho-family small GTPases before and after forskolin treatment has been evaluated with a glutathione-S-transferase pull-down
assay. Forskolin reinforces the integrity of cell-cell contacts, resulting in the closure of an intercellular adhesion zipper,
accompanied by a redistribution of cell adhesion molecules and actin-associated proteins in a continuous linear pattern at
cell-cell contacts. The Rho-family small GTPases Rac1 and Cdc42 are activated during closure of the adhesion zipper, whereas
RhoA is suppressed. Thus, cAMP promotes the assembly of cell-cell contacts between podocytes via a mechanism that probably
involves Rho-family small GTPases.
This study was supported in part by a grant-in-aid for scientific research from the Japanese Ministry for Education, Culture,
Sports, Science, and Technology (to N. K., no. 14570015). S-Y.G. is a recipient of a grant awarded by the Japanese government
to graduate students from foreign countries. 相似文献
49.
Ali HI Tomita K Akaho E Kambara H Miura S Hayakawa H Ashida N Kawashima Y Yamagishi T Ikeya H Yoneda F Nagamatsu T 《Bioorganic & medicinal chemistry》2007,15(1):242-256
Novel 2-deoxo-2-phenyl-5-deazaflavins and 2-deoxo-2-phenylflavin-5-oxides were prepared as a new class of antitumor agents and showed significant antitumor activities against NCI-H 460, HCT 116, A 431, CCRF-HSB-2, andKB cell lines. In vivo investigation, 2-deoxo-10-methyl-2-phenyl-5-deazaflavin exhibited the effective antitumor activity against A 431 human adenocarcinoma cells transplanted subcutaneously into nude mouse. Furthermore, AutoDock study has been done by binding of the flavin analogs into PTK pp60(c-src), where a good correlation between their IC(50) and AutoDock binding free energy was exhibited. In particular, 2-deoxo-2-phenylflavin-5-oxides exhibited the highest potential binding affinity within the binding pocket of PTK. 相似文献
50.
Kashiwagi T Wu B Iyota K Chen XH Tebayashi SI Kim CS 《Bioscience, biotechnology, and biochemistry》2007,71(4):966-970
(1S,6R)-2,7(14),10-bisabolatrien-1-ol-4-one and (+)-7(14),10-bisaboladien-1-ol-4-one were isolated and identified from Cryptomeria japonica as antifeedants against Locusta migratoria L. which is well known as a serious pest to cereals throughout the world. These compounds strongly inhibited the feeding of L. migratoria only when they were combined, but each compound alone did not show any activity. 相似文献