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991.
Masashi Kawamura Michael J. Paulsen Andrew B. Goldstone Yasuhiro Shudo Hanjay Wang Amanda N. Steele Lyndsay M. Stapleton Bryan B. Edwards Anahita Eskandari Vi N. Truong Kevin J. Jaatinen Arnar B. Ingason Shigeru Miyagawa Yoshiki Sawa Y. Joseph Woo 《Cardiovascular diabetology》2017,16(1):142
Background
Diabetes mellitus is a risk factor for coronary artery disease and diabetic cardiomyopathy, and adversely impacts outcomes following coronary artery bypass grafting. Current treatments focus on macro-revascularization and neglect the microvascular disease typical of diabetes mellitus-induced cardiomyopathy (DMCM). We hypothesized that engineered smooth muscle cell (SMC)-endothelial progenitor cell (EPC) bi-level cell sheets could improve ventricular dysfunction in DMCM.Methods
Primary mesenchymal stem cells (MSCs) and EPCs were isolated from the bone marrow of Wistar rats, and MSCs were differentiated into SMCs by culturing on a fibronectin-coated dish. SMCs topped with EPCs were detached from a temperature-responsive culture dish to create an SMC-EPC bi-level cell sheet. A DMCM model was induced by intraperitoneal streptozotocin injection. Four weeks after induction, rats were randomized into 3 groups: control (no DMCM induction), untreated DMCM, and treated DMCM (cell sheet transplant covering the anterior surface of the left ventricle).Results
SMC-EPC cell sheet therapy preserved cardiac function and halted adverse ventricular remodeling, as demonstrated by echocardiography and cardiac magnetic resonance imaging at 8 weeks after DMCM induction. Myocardial contrast echocardiography demonstrated that myocardial perfusion and microvascular function were preserved in the treatment group compared with untreated animals. Histological analysis demonstrated decreased interstitial fibrosis and increased microvascular density in the SMC-EPC cell sheet-treated group.Conclusions
Treatment of DMCM with tissue-engineered SMC-EPC bi-level cell sheets prevented cardiac dysfunction and microvascular disease associated with DMCM. This multi-lineage cellular therapy is a novel, translatable approach to improve microvascular disease and prevent heart failure in diabetic patients.992.
Tsutomu Shimura Megumi Sasatani Hidehiko Kawai Kenji Kamiya Junya Kobayashi Kenshi Komatsu 《Cell cycle (Georgetown, Tex.)》2017,16(6):565-573
Mitochondria play a key role in maintaining cellular homeostasis during stress responses, and mitochondrial dysfunction contributes to carcinogenesis, aging, and neurologic disease. We here investigated ionizing radiation (IR)-induced mitochondrial damage in human neural progenitor stem cells (NSCs), their differentiated counterparts and human normal fibroblasts. Long-term fractionated radiation (FR) with low doses of X-rays for 31 d enhanced mitochondrial activity as evident by elevated mitochondrial membrane potential (ΔΨm) and mitochondrial complex IV (cytochrome c oxidase) activity to fill the energy demands for the chronic DNA damage response in differentiated cells. Subsequent reduction of the antioxidant glutathione via continuous activation of mitochondrial oxidative phosphorylation caused oxidative stress and genomic instability in differentiated cells exposed to long-term FR. In contrast, long-term FR had no effect on the mitochondrial activity in NSCs. This cell type showed efficient DNA repair, no mitochondrial damage, and resistance to long-term FR. After high doses of acute single radiation (SR) (> 5 Gy), cell cycle arrest at the G2 phase was observed in NSCs and human fibroblasts. Under this condition, increase in mitochondria mass, mitochondrial DNA, and intracellular reactive oxygen species (ROS) levels were observed in the absence of enhanced mitochondrial activity. Consequently, cellular senescence was induced by high doses of SR in differentiated cells.
In conclusion, we demonstrated that mitochondrial radiation responses differ according to the extent of DNA damage, duration of radiation exposure, and cell differentiation. 相似文献
993.
Endoplasmic reticulum stress-inducible protein, Herp, enhances presenilin-mediated generation of amyloid beta-protein. 总被引:7,自引:0,他引:7
Xiaorei Sai Yuuki Kawamura Koichi Kokame Haruyasu Yamaguchi Hirohisa Shiraishi Ryo Suzuki Toshiharu Suzuki Masashi Kawaichi Toshiyuki Miyata Toshio Kitamura Bart De Strooper Katsuhiko Yanagisawa Hiroto Komano 《The Journal of biological chemistry》2002,277(15):12915-12920
Presenilin (PS) is essential for the gamma-cleavage required for the generation of the C terminus of amyloid beta-protein (Abeta). However, the mechanism underlying PS-mediated gamma-cleavage remains unclear. We have identified Herp cDNA by our newly developed screening method for the isolation of cDNAs that increase the degree of gamma-cleavage. Herp was originally identified as a homocysteine-responsive protein, and its expression is up-regulated by endoplasmic reticulum stress. Herp is an endoplasmic reticulum-localized membrane protein that has a ubiquitin-like domain. Here, we report that a high expression of Herp in cells increases the level of Abeta generation, although not in PS-deficient cells. We found that Herp interacts with both PS1 and PS2. Thus, Herp regulates PS-mediated Abeta generation, possibly through its binding to PS. Immunohistochemical analysis of a normal human brain section with an anti-Herp antibody revealed the exclusive staining of neurons and vascular smooth muscle cells. Moreover, the antibody strongly stained activated microglia in senile plaques in the brain of patients with Alzheimer disease. Taken together, Herp could be involved in Abeta accumulation, including the formation of senile plaques and vascular Abeta deposits. 相似文献
994.
Rho/ROCK pathway contributes to the activation of extracellular signal-regulated kinase/GATA-4 during myocardial cell hypertrophy. 总被引:5,自引:0,他引:5
995.
Megumi Akita Masayoshi Kuwahara Ryoji Nishibata Hiroki Mikami Hirokazu Tsubone 《Experimental Animals》2004,53(2):121-127
We studied the characteristics of the rhythmicity of heart rate (HR), body temperature (BT), locomotor activity (LA) and autonomic nervous activity in bronchial-hypersensitive (BHS) and bronchial-hyposensitive (BHR) guinea pigs. For this purpose, HR, BT, LA, and electrocardiogram (ECG) were recorded from conscious and unrestrained guinea pigs using a telemetry system. Autonomic nervous activity was analyzed by power spectral analysis of heart rate variability. Nocturnal patterns, in which the values in the dark phase (20:00-06:00) were higher than those in the light phase (06:00-20:00), were observed in HR, BT and LA in both strains of guinea pigs. The autonomic nervous activity in BHS guinea pigs showed a daily pattern, although BHR guinea pigs did not show such a rhythmicity. The high frequency (HF) power in BHS guinea pigs was higher than that in BHR guinea pigs throughout the day. Moreover, the low frequency/high frequency (LF/HF) ratio in BHS guinea pigs was lower than that in BHR guinea pigs throughout the day. These results suggest that parasympathetic nervous activity may be predominant in BHS guinea pigs. 相似文献
996.
Jun Yamanouchi Atsushi Takatori Etsuko Nishida Seiji Kawamura Yasuhiro Yoshikawa 《Experimental Animals》2002,51(1):33-41
Syrian hamsters of the APA strain (APA hamsters) have recently been demonstrated to develop atheromatous lesions in the aortic arches under the diabetic condition induced by a single injection of streptozotocin (SZ). Various lipoprotein receptors are reported to play important roles in atherogenesis mainly in vitro, while there are few reports on the relative expressions of these receptors in vivo. In this study, we therefore examined messenger RNA (mRNA) expressions of several lipoprotein receptors on the aortic arches of diabetic APA hamsters at 6, 14 and 26 weeks after the injection (WAI) of SZ. In semi-quantitative RT-PCR, scavenger receptor (SR)-AI, macrosialin (MS)/CD68, and receptor for advanced glycation end-products (RAGE) mRNAs showed significant increases at 6 WAI of SZ, and SR-AI and CD36 mRNA obviously increased until 26 WAI, as compared with the control. Low-density lipoprotein receptor mRNA showed a significant decrease at 14 and 26 WAI, and SR-BI mRNA significantly decreased at 6 and 14 WAI, as compared with the control. Very low-density lipoprotein receptor mRNA was at the same level as the control. By means of in situ hybridization, SR-AI, MS/CD68 and RAGE mRNA were detected in the foam cells of the fatty streaks at 6 WAI, which suggested that SR-AI, MS/CD68 and RAGE play crucial roles in the formation of the fatty streaks, the initial lesions of atherogenesis in diabetic APA hamsters. SR-AI and CD36 were also believed to be related to the progression of atherogenesis in this model. 相似文献
997.
Summary Guadalupian reefs occur locally in Guangxi, Guizhou, Yunnan and Western Zhejiang, South China. Two types of Guadalupian reefs
can be recognized, one is developed in carbonate platforms, e.g. those in the juncture areas of Guangxi, Yunnan and Guizhou;
the other occurs in a littoral clastic shelf. The Lengwu reef in Western Zhejiang is a representative of the latter type,
which is a major topic of this paper. Lengwu algae-sponge reef, more than one hundred meters in thickness, are composed mainly
of sponges, hydrozoans, algae, bryozoans, microbes and lime mud. Reef limestones sit on the mudstone interbedded with fine
sandstone of the proximal prodelta facies and are overlain by coarse clasts of the delta front sediments. Lengwu reef displays
a lens-shaped relief, dipping and thinning from the reef core, which is remarkably different from the surrounding sediments,
showing a protruding relief. Sponges and microbe/algae form bafflestone, bindstone and framestone of the reef core facies.
Fore-reef facies is characterized by lithoclastic rudstone and bioclastic packstone. Reef limestone sequence is composed of
three cycles and controlled by sea level changes and sediment influx. Such reef is unique among the Guadalupian reefs in South
China, but seems similar in some aspects to Iwaizaki reef limestones of south Kitakami in Japan. Algae and microbes growing
around sponges to form rigid structure in Lengwu reef are a typical feature, which is distinctly different to Guadalupian
reefs in a stable platform facies of Guizhou, Yunnan and Guangxi, South China. 相似文献
998.
Tomiko Asano Haruo Shinohara † Rika Morishita Hiroshi Ueda Noriko Kawamura Ritsuko Katoh-Semba Masao Kishikawa Kanefusa Kato 《Journal of neurochemistry》2001,79(6):1129-1135
G proteins play important roles in transmembrane signal transduction, and various isoforms of each subunit, alpha, beta and gamma, are highly expressed in the brain. The Ggamma5 subunit is a minor isoform in the adult brain, but we have previously shown it to be highly expressed in the proliferative region of the ventricular zone in the rat embryonic brain. We show here that Ggamma5 is also selectively localized in a proliferative region in the adult rat brain, including the subventricular zone of the lateral ventricle and rostral migratory stream. The Galphai2 subunit colocalized with Ggamma5 in these regions, the two subunits being present in neuronal precursors and ependymal cells but not in proliferating astrocytes. In addition, intense staining of Ggamma5 was seen in axons of the olfactory neurons, which are known to regenerate. These results suggest specific roles for Ggamma5 in precursor cells during neurogenesis so that this isoform might be a useful biological marker. 相似文献
999.
K Ishiwata Y Koyanagi K Abe K Kawamura K Taguchi T Saitoh J Toda M Senda T Sano 《Journal of neurochemistry》2001,79(4):868-876
Parkinsonism-inducing neurotoxicity of 1,2,3,4-tetrahydroisoquinoline (TIQ), as contrasted to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), and parkinsonism-preventing effect of 1-methyl-1,2,3,4-tetrahydroisoquinoline (1-MeTIQ) have been investigated in mice by measuring their effects on the in vivo binding of radioligand to pre-synaptic dopamine transporters (DATs) or to dopamine D(2) receptors (D2R) in the striatum. A significant reduction of the ligand-DATs binding was found in the mice treated with MPTP, but not with TIQ, under the dosage inducing behavioral abnormality and loss of tyrosine hydroxylase-positive cells in the substantia nigra. A slight decrease in the ligand-DATs binding was observed in the mice given a larger dose of TIQ. Compensatory up-regulation in the post-synaptic D2Rs was found in the MPTP-treated mice. Pre-treatment with (S)-enantiomer, but not (R)-enantiomer, of 1-MeTIQ prevented the degeneration of DATs to some extent. We concluded that the TIQ-induced parkinsonism model is different from the MPTP-induced model as evaluated by the radioligand-DATs binding and that (S)-1-MeTIQ has a preventing effect for the degeneration of the DATs to a certain extent. 相似文献
1000.
Y Kawamura A Kikuchi R Takada S Takada S Sudoh S Shibamoto K Yanagisawa H Komano 《European journal of biochemistry》2001,268(10):3036-3041
Mutations in the presenilin 1 (PS1) gene are the most common genetic factor underlying the development of early onset familial Alzheimer's disease (FAD). Accumulating evidence has shown that FAD-linked mutations of PS1 enhance the generation of amyloid-beta (1-42) protein. Recently, beta-catenin has been shown to interact with PS1. beta-catenin is essential for the Wnt signalling pathway. However, the biological significance of the interaction between beta-catenin and PS1 in this signalling pathway remains to be clarified. In this study, we investigated the effect of FAD-linked PS1 (M146L) mutation in the Wnt signalling pathway using the conditioned medium containing Wnt-3A. The expression of mutated PS1 inhibited the Wnt-3A-induced accumulation of beta-catenin. Chase analysis of beta-catenin in Wnt-3A-stimulated cells following cycloheximide treatment revealed that PS1 mutation enhanced the generation of the higher molecular mass form of beta-catenin, most likely, ubiquitinated beta-catenin. In addition, the expression of mutated PS1 elevated the level of phosphorylated beta-catenin, which is targeted to the ubiquitin/proteasome pathway. Thus, it appears that PS1 (M146L) mutation down-regulates the Wnt-3A-induced accumulation of beta-catenin due to an increase in the level of phosphorylated beta-catenin. 相似文献