全文获取类型
收费全文 | 723篇 |
免费 | 35篇 |
出版年
2023年 | 4篇 |
2022年 | 3篇 |
2021年 | 13篇 |
2020年 | 3篇 |
2019年 | 7篇 |
2018年 | 14篇 |
2017年 | 12篇 |
2016年 | 20篇 |
2015年 | 26篇 |
2014年 | 20篇 |
2013年 | 49篇 |
2012年 | 65篇 |
2011年 | 61篇 |
2010年 | 33篇 |
2009年 | 37篇 |
2008年 | 53篇 |
2007年 | 39篇 |
2006年 | 54篇 |
2005年 | 43篇 |
2004年 | 50篇 |
2003年 | 24篇 |
2002年 | 37篇 |
2001年 | 3篇 |
2000年 | 10篇 |
1999年 | 5篇 |
1998年 | 6篇 |
1997年 | 9篇 |
1996年 | 5篇 |
1995年 | 4篇 |
1994年 | 8篇 |
1993年 | 6篇 |
1992年 | 4篇 |
1991年 | 1篇 |
1990年 | 3篇 |
1988年 | 4篇 |
1985年 | 1篇 |
1984年 | 3篇 |
1983年 | 3篇 |
1982年 | 1篇 |
1981年 | 2篇 |
1980年 | 2篇 |
1979年 | 1篇 |
1978年 | 2篇 |
1977年 | 2篇 |
1974年 | 1篇 |
1973年 | 2篇 |
1970年 | 1篇 |
1969年 | 1篇 |
1968年 | 1篇 |
排序方式: 共有758条查询结果,搜索用时 15 毫秒
711.
Sekine M Monkawa T Morizane R Matsuoka K Taya C Akita Y Joh K Itoh H Hayashi M Kikkawa Y Kohno K Suzuki A Yonekawa H 《Transgenic research》2012,21(1):51-62
The proximal straight tubule (S3 segment) of the kidney is highly susceptible to ischemia and toxic insults but has a remarkable capacity to repair its structure and function. In response to such injuries, complex processes take place to regenerate the epithelial cells of the S3 segment; however, the precise molecular mechanisms of this regeneration are still being investigated. By applying the ??toxin receptor mediated cell knockout?? method under the control of the S3 segment-specific promoter/enhancer, Gsl5, which drives core 2 ??-1,6-N-acetylglucosaminyltransferase gene expression, we established a transgenic mouse line expressing the human diphtheria toxin (DT) receptor only in the S3 segment. The administration of DT to these transgenic mice caused the selective ablation of S3 segment cells in a dose-dependent manner, and transgenic mice exhibited polyuria containing serum albumin and subsequently developed oliguria. An increase in the concentration of blood urea nitrogen was also observed, and the peak BUN levels occurred 3?C7?days after DT administration. Histological analysis revealed that the most severe injury occurred in the S3 segments of the proximal tubule, in which tubular cells were exfoliated into the tubular lumen. In addition, aquaporin 7, which is localized exclusively to the S3 segment, was diminished. These results indicate that this transgenic mouse can suffer acute kidney injury (AKI) caused by S3 segment-specific damage after DT administration. This transgenic line offers an excellent model to uncover the mechanisms of AKI and its rapid recovery. 相似文献
712.
Density-dependent mortality has been considered a symptom of intraspecific competition. We examined the occurrence of such
mortality in the early stages of gall induction by the gall midge Asphondylia aucubae Yukawa et Ohsaki (Diptera: Cecidomyiidae). Female midges deposit eggs into young fruit of the dioecious shrub Aucuba japonica Thunberg to induce gall formation. Each host fruit received 0–67 eggs (mean 18.5 eggs) from multiple females, whereas established
galls each contained one to ten larvae. Midges suffered intense mortality (65–90%) at the egg stage. Egg mortality occurred
even in fruit in which no larvae had hatched, suggesting that this mortality cannot be wholly attributed to larval interference.
Egg mortality was affected by fruit size, i.e., resource capacity. Midges distributed more eggs in larger fruit. Egg mortality
increased as the per-fruit density increased relative to fruit size. In contrast, the mortality of hatchlings was density-independent.
Our results suggest that A. aucubae intensely compete for gall-induction substrates, which are spatiotemporally rare resources. 相似文献
713.
Increased expression of the auxin-inducible gene PsIAA4/5 was observed in the elongated side of epicotyls in early growth stages of etiolated pea (Pisum sativum L. cv. Alaska) seedlings grown in a horizontal or an inclined position under 1 g conditions. Under simulated microgravity conditions on a 3D clinostat, accumulation of PsIAA4/5 mRNA was found throughout epicotyls showing automorphosis. Polar auxin transport in the proximal side of epicotyls changed
when the seedlings were grown in a horizontal or an inclined position under 1 g conditions, but that under clinorotation did not, regardless of the direction of seed setting. Accumulation of PsPIN1 and PsPIN2 mRNAs in epicotyls was affected by gravistimulation, but not by clinorotation. Under 1 g conditions, auxin-transport inhibitors made epicotyls of seedlings grown in a horizontal or inclined position grow toward
the proximal direction to cotyledons. These inhibitors led to epicotyl bending toward the cotyledons in seedlings grown in
an inclined position under clinorotation. Polar auxin transport, as well as growth direction, of epicotyls of the agravitropic
mutant ageotropum did not respond to various gravistimulation. These results suggest that alteration of polar auxin transport in the proximal
side of epicotyls regulates the graviresponse of pea epicotyls. 相似文献
714.
Sasaki S Inoguchi T Muta K Abe Y Zhang M Hiasa K Egashira K Sonoda N Kobayashi K Takayanagi R Nawata H 《American journal of physiology. Heart and circulatory physiology》2007,292(1):H657-H665
Recent reports have demonstrated that erythroid progenitor cells contain and secrete various angiogenic cytokines. Here, the impact of erythroid colony-forming cell (ECFC) implantation on therapeutic angiogenesis was investigated in murine models of hindlimb ischemia. During the in vitro differentiation, vascular endothelial growth factor (VEGF) secretion by ECFCs was observed from day 3 (burst-forming unit erythroid cells) to day 10 (erythroblasts). ECFCs from day 5 to day 7 (colony-forming unit erythroid cells) showed the highest VEGF productivity, and day 6 ECFCs were used for the experiments. ECFCs contained larger amounts of VEGF and fibroblast growth factor-2 (FGF-2) than peripheral blood mononuclear cells (PBMNCs). In tubule formation assays with human umbilical vein endothelial cells, ECFCs stimulated 1.5-fold more capillary growth than PBMNCs, and this effect was suppressed by antibodies against VEGF and FGF-2. Using an immunodeficient hindlimb ischemia model and laser-Doppler imaging, we evaluated the limb salvage rate and blood perfusion after intramuscular implantation of ECFCs. ECFC implantation increased both the salvage rate (38% vs. 0%, P < 0.05) and the blood perfusion (82.8% vs. 65.6%, P < 0.01). In addition, ECFCs implantation also significantly increased capillaries with recruitment of vascular smooth muscle cells and the capillary density was 1.6-fold higher than in the control group. Continuous production of human VEGF from ECFCs in the skeletal muscle was confirmed at least 7 days after the implantation. Implantation of ECFCs promoted angiogenesis in ischemic limbs by supplying angiogenic cytokines (VEGF and FGF-2), suggesting a possible novel strategy for therapeutic angiogenesis. 相似文献
715.
716.
Kenichiro Hanawa Kenta Ito Kentaro Aizawa Tomohiko Shindo Kensuke Nishimiya Yuhi Hasebe Ryuji Tuburaya Hideyuki Hasegawa Satoshi Yasuda Hiroshi Kanai Hiroaki Shimokawa 《PloS one》2014,9(8)
Background
Although a significant progress has been made in the management of ischemic heart disease (IHD), the number of severe IHD patients is increasing. Thus, it is crucial to develop new, non-invasive therapeutic strategies. In the present study, we aimed to develop low-intensity pulsed ultrasound (LIPUS) therapy for the treatment of IHD.Methods and Results
We first confirmed that in cultured human endothelial cells, LIPUS significantly up-regulated mRNA expression of vascular endothelial growth factor (VEGF) with a peak at 32-cycle (P<0.05). Then, we examined the in vivo effects of LIPUS in a porcine model of chronic myocardial ischemia with reduced left ventricular ejection fraction (LVEF) (n = 28). The heart was treated with either sham (n = 14) or LIPUS (32-cycle with 193 mW/cm2 for 20 min, n = 14) at 3 different short axis levels. Four weeks after the treatment, LVEF was significantly improved in the LIPUS group (46±4 to 57±5%, P<0.05) without any adverse effects, whereas it remained unchanged in the sham group (46±5 to 47±6%, P = 0.33). Capillary density in the ischemic region was significantly increased in the LIPUS group compared with the control group (1084±175 vs. 858±151/mm2, P<0.05). Regional myocardial blood flow was also significantly improved in the LIPUS group (0.78±0.2 to 1.39±0.4 ml/min/g, P<0.05), but not in the control group (0.84±0.3 to 0.97±0.4 ml/min/g). Western blot analysis showed that VEGF, eNOS and bFGF were all significantly up-regulated only in the LIPUS group.Conclusions
These results suggest that the LIPUS therapy is promising as a new, non-invasive therapy for IHD. 相似文献717.
Kenichi Konda Kazuo Konishi Toshiko Yamochi Yoichi M. Ito Hisako Nozawa Masayuki Tojo Kensuke Shinmura Mari Kogo Atsushi Katagiri Yutaro Kubota Takashi Muramoto Yuichiro Yano Yoshiya Kobayashi Toshihiro Kihara Teppei Tagawa Reiko Makino Masafumi Takimoto Michio Imawari Hitoshi Yoshida 《PloS one》2014,9(8)
Background
Colorectal adenoma develops into cancer with the accumulation of genetic and epigenetic changes. We studied the underlying molecular and clinicopathological features to better understand the heterogeneity of colorectal neoplasms (CRNs).Methods
We evaluated both genetic (mutations of KRAS, BRAF, TP53, and PIK3CA, and microsatellite instability [MSI]) and epigenetic (methylation status of nine genes or sequences, including the CpG island methylator phenotype [CIMP] markers) alterations in 158 CRNs including 56 polypoid neoplasms (PNs), 25 granular type laterally spreading tumors (LST-Gs), 48 non-granular type LSTs (LST-NGs), 19 depressed neoplasms (DNs) and 10 small flat-elevated neoplasms (S-FNs) on the basis of macroscopic appearance.Results
S-FNs showed few molecular changes except SFRP1 methylation. Significant differences in the frequency of KRAS mutations were observed among subtypes (68% for LST-Gs, 36% for PNs, 16% for DNs and 6% for LST-NGs) (P<0.001). By contrast, the frequency of TP53 mutation was higher in DNs than PNs or LST-Gs (32% vs. 5% or 0%, respectively) (P<0.007). We also observed significant differences in the frequency of CIMP between LST-Gs and LST-NGs or PNs (32% vs. 6% or 5%, respectively) (P<0.005). Moreover, the methylation level of LINE-1 was significantly lower in DNs or LST-Gs than in PNs (58.3% or 60.5% vs. 63.2%, P<0.05). PIK3CA mutations were detected only in LSTs. Finally, multivariate analyses showed that macroscopic morphologies were significantly associated with an increased risk of molecular changes (PN or LST-G for KRAS mutation, odds ratio [OR] 9.11; LST-NG or DN for TP53 mutation, OR 5.30; LST-G for PIK3CA mutation, OR 26.53; LST-G or DN for LINE-1 hypomethylation, OR 3.41).Conclusion
We demonstrated that CRNs could be classified into five macroscopic subtypes according to clinicopathological and molecular differences, suggesting that different mechanisms are involved in the pathogenesis of colorectal tumorigenesis. 相似文献718.
Atsushi Suzuki Hiroyuki Taniguchi Naohiro Watanabe Yasuhiro Kondoh Tomoki Kimura Kensuke Kataoka Toshiaki Matsuda Toshiki Yokoyama Koji Sakamoto Osamu Nishiyama Yoshinori Hasegawa 《PloS one》2014,9(9)
Background
Lung-dominant connective tissue disease (LD-CTD) is a new concept for classifying the subset of patients with interstitial pneumonia who have clinical features suggesting an associated CTD, but whose features fall short of a clear diagnosis of CTD under the current rheumatologic classification systems. The impact of mean pulmonary arterial pressure (MPAP) in LD-CTD has not been sufficiently elucidated.Objectives
To evaluate the survival impact of MPAP measured during the initial evaluation in patients with LD-CTD.Methods
We retrospectively analyzed the initial evaluation data of 100 LD-CTD patients undergoing pulmonary function test, 6-min walk test (6MWT), and right heart catheterization (RHC).Results
The mean MPAP was 16.2±4.4 mm Hg, and 18 patients had MPAP≥20 mm Hg. A univariate Cox proportional hazard model showed that MPAP and several variables have a statistically significant impact on survival. With stepwise, multivariate Cox proportional analysis, MPAP (HR = 1.293; 95% CI 1.130–1.480; p<0.001) and mean forced vital capacity (FVC) % predicted (HR = 0.958; 95% CI 0.930–0.986; p = 0.004) were shown to be independent determinants of survival.Conclusions
Higher MPAP and lower %FVC at the initial evaluation were significant independent prognostic factors of LD-CTD. MPAP evaluation provides additional information of disease status and will help physicians to predict mortality in LD-CTD. 相似文献719.
Tetsuo Fujita Kento Yoshioka Hiroki Umezawa Kensuke Tanaka Yusuke Naito Toshinori Nakayama Masahiko Hatano Koichiro Tatsumi Yoshitoshi Kasuya 《Biochemistry and Biophysics Reports》2016
Cluster of differentiation 69 (CD69), known as an early activation marker of lymphocytes, has been demonstrated to regulate inflammatory events in various disease models. Although the increased number of CD69-expressed T lymphocytes in the lungs of patients with chronic obstructive pulmonary disease (COPD) has been reported, a functional role of CD69 in the pathogenesis of COPD remains unknown. To address to this question, CD69-deficient (CD69KO) mice and wild-type (WT) mice were subjected to a mouse model of porcine pancreatic elastase (PPE)-induced pulmonary inflammation and emphysema. In the two genotypes, PPE increased counts of macrophages, neutrophils and lymphocytes in bronchoalveolar lavage fluid (BALF) and induced emphysematous changes in the lung, whereas those two pathological signs were significantly enhanced in CD69KO mice compared to WT mice. Moreover, the PPE-induced levels of IL-17 and IL-6 in BALF were significantly higher in CD69KO mice than in WT mice at the acute inflammatory phase. Immunofluorescent studies showed that IL-17 and IL-6 were predominantly expressed in CD4+ and γδ T cells and macrophages, respectively. Concomitant administration of IL-17- and IL-6-neutralizing antibodies significantly attenuated the PPE-induced emphysematous changes in the two genotypes. These findings suggest that CD69 negatively regulates the development of PPE-induced emphysema in part at least through modulating function of IL-17-producing T cells. 相似文献
720.
Parameterisation and validation of a resource budget model for masting using spatiotemporal flowering data of individual trees 下载免费PDF全文
Tomoyuki Abe Yuuya Tachiki Hirokazu Kon Akiko Nagasaka Kensuke Onodera Kazuhiro Minamino Qingmin Han Akiko Satake 《Ecology letters》2016,19(9):1129-1139
Synchronised and fluctuating reproduction by plant populations, called masting, is widespread in diverse taxonomic groups. Here, we propose a new method to explore the proximate mechanism of masting by combining spatiotemporal flowering data, biochemical analysis of resource allocation and mathematical modelling. Flowering data of 170 trees over 13 years showed the emergence of clustering with trees in a given cluster mutually synchronised in reproduction, which was successfully explained by resource budget models. Analysis of resources invested in the development of reproductive organs showed that parametric values used in the model are significantly different between nitrogen and carbon. Using a fully parameterised model, we showed that the observed flowering pattern is explained only when the interplay between nitrogen dynamics and climatic cues was considered. This result indicates that our approach successfully identified resource type‐specific roles on masting and that the method is suitable for a wide range of plant species. 相似文献