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Hiroto Ueba Masashi Shiomi Michael Brines Michael Yamin Tsutomu Kobayashi Junya Ako Shin-ichi Momomura Anthony Cerami Masanobu Kawakami 《Molecular medicine (Cambridge, Mass.)》2013,19(1):195-202
Erythropoietin (EPO), a type I cytokine originally identified for its critical role in hematopoiesis, has been shown to have nonhematopoietic, tissue-protective effects, including suppression of atherosclerosis. However, prothrombotic effects of EPO hinder its potential clinical use in nonanemic patients. In the present study, we investigated the antiatherosclerotic effects of helix B surface peptide (HBSP), a nonerythropoietic, tissue-protective compound derived from EPO, by using human umbilical vein endothelial cells (HUVECs) and human monocytic THP-1 cells in vitro and Watanabe heritable hyperlipidemic spontaneous myocardial infarction (WHHLMI) rabbits in vivo. In HUVECs, HBSP inhibited apoptosis (≈70%) induced by C-reactive protein (CRP), a direct mediator of atherosclerosis. By using a small interfering RNA approach, Akt was shown to be a key molecule in HBSP-mediated prevention of apoptosis. HBSP also attenuated CRP-induced production of tumor necrosis factor (TNF)-α and matrix metalloproteinase-9 in THP-1 cells. In the WHHLMI rabbit, HBSP significantly suppressed progression of coronary atherosclerotic lesions as assessed by mean cross-sectional stenosis (HBSP 21.3 ± 2.2% versus control peptide 38.0 ± 2.7%) and inhibited coronary artery endothelial cell apoptosis with increased activation of Akt. Furthermore, TNF-α expression and the number of M1 macrophages and M1/M2 macrophage ratio in coronary atherosclerotic lesions were markedly reduced in HBSP-treated animals. In conclusion, these data demonstrate that HBSP suppresses coronary atherosclerosis, in part by inhibiting endothelial cell apoptosis through activation of Akt and in association with decreased TNF-α production and modified macrophage polarization in coronary atherosclerotic lesions. Because HBSP does not have the prothrombotic effects of EPO, our study may provide a novel therapeutic strategy that prevents progression of coronary artery disease. 相似文献
74.
Hiroyuki Kajiura Masashi Wasai Saori Kasahara Fumio Takaiwa Kazuhito Fujiyama 《Molecular biotechnology》2013,54(3):784-794
Cholera toxin B subunit (CTB) is widely used as a carrier molecule and mucosal adjuvant and for the expression of fusion proteins of interest. CTB-fusion proteins are also expressed in plants, but the N-glycan structures of CTB have not been clarified. To gain insights into the N-glycosylation and N-glycans of CTB expressed in plants, we expressed CTB in rice seeds with an N-terminal glutelin signal and a C-terminal KDEL sequence and analyzed its N-glycosylation and N-glycan structures. CTB was successfully expressed in rice seeds in two forms: a form with N-glycosylation at Asn32 that included both plant-specific N-glycans and small oligomannosidic N-glycans and a non-N-glycosylated form. N-Glycan analysis of CTB showed that approximately 50 % of the N-glycans had plant-specific M3FX structures and that almost none of the N-glycans was of high-mannose-type N-glycan even though the CTB expressed in rice seeds contains a C-terminal KDEL sequence. These results suggest that the CTB expressed in rice was N-glycosylated through the endoplasmic reticulum (ER) and Golgi N-glycosylation machinery without the ER retrieval. 相似文献
75.
Yuriko Saito Ippei Takahashi Kaori Iwane Noriyuki Okubo Miya Nishimura Masashi Matsuzaka Naoko Wada Takashi Miwa Takashi Umeda Shigeyuki Nakaji 《Luminescence》2013,28(4):569-573
We assessed the association of neutrophil function with glycated hemoglobin (HbA1c) levels in a Japanese general population. Participants were 809 males and females who were over 20 years old living in the Iwaki region in Aomori Prefecture located in northern Japan. Lifestyle parameters (smoking, alcohol consumption, and exercise habits), HbA1c and neutrophil function such as reactive oxygen species (ROS) production capability and phagocytic activity (PA) were measured. ROS production capability was measured before and after phagocytic stimulus to obtain basal ROS production and stimulated ROS production. Level of HbA1c had a positive correlation with basal ROS production (p=0.053), a negative correlation with stimulated ROS production (p=0.072) and PA (p=0.059) only in post‐menopausal groups, and not in pre‐menopausal groups. However, there were no correlations between levels of HbA1c and neutrophil functions in male. In conclusion, in the present study, despite the presence of diabetes, chronic hyperglycemia was found to cause an increase in daily basal ROS production of neutrophils, and increased susceptibility to infection caused by reduced neutrophilic reaction in females in their menopause. Therefore, from the oxidative point of view, strict glycemic control is necessary to prevent post‐menopausal females from developing diabetic complications in spite of the presence of diabetes. 相似文献
76.
Kentaro Uchida Kouji Naruse Masashi Satoh Kenji Onuma Masaki Ueno Shotaro Takano Ken Urabe Masashi Takaso 《Experimental Animals》2013,62(3):255-265
Although recent studies suggest that hyperlipidemia is a risk factor for osteoarthritis
(OA), the link between OA and hyperlipidemia is not fully understood. As the number of
activated, circulating myeloid cells is increased during hyperlipidemia, we speculate that
myeloid cells contribute to the pathology of OA. Here, we characterized myeloid cells in
STR/Ort mice, a murine osteoarthritis model, under hyperlipidemic conditions. Ratios of
myeloid cells in bone marrow, the spleen, and peripheral blood were determined by flow
cytometry. To examine the influence of the hematopoietic environment, including abnormal
stem cells, on the hematopoietic profile of STR/Ort mice, bone marrow transplantations
were performed. The relationship between hyperlipidemia and abnormal hematopoiesis was
examined by evaluating biochemical parameters and spleen weight of F2 animals
(STR/Ort x C57BL/6J). In STR/Ort mice, the ratio of CD11b+Gr1+ cells
in spleens and peripheral blood was increased, and CD11b+Gr1+ cells
were also present in synovial tissue. Splenomegaly was observed and correlated with the
ratio of CD11b+Gr1+ cells. When bone marrow from GFP-expressing mice
was transplanted into STR/Ort mice, no difference in the percentage of
CD11b+Gr1+ cells was observed between transplanted and age-matched
STR/Ort mice. Analysis of biochemical parameters in F2 mice showed that spleen
weight correlated with serum total cholesterol. These results suggest that the increase in
circulating and splenic CD11b+Gr1+ cells in STR/Ort mice originates
from hypercholesterolemia. Further investigation of the function of
CD11b+Gr1+ cells in synovial tissue may reveal the pathology of OA
in STR/Ort mice. 相似文献
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78.
Masashi Kato Mayuko Y. Kumasaka Shoko Ohnuma Akio Furuta Yoko Kato Hossain U. Shekhar Michiyo Kojima Yasuko Koike Nguyen Dinh Thang Nobutaka Ohgami Thuy Bich Ly Xiaofang Jia Husna Yetti Hisao Naito Gaku Ichihara Ichiro Yajima 《PloS one》2013,8(6)
Health risk for well drinking water is a worldwide problem. Our recent studies showed increased toxicity by exposure to barium alone (≤700 µg/L) and coexposure to barium (137 µg/L) and arsenic (225 µg/L). The present edition of WHO health-based guidelines for drinking water revised in 2011 has maintained the values of arsenic (10 µg/L) and barium (700 µg/L), but not elements such as manganese, iron and zinc. Nevertheless, there have been very few studies on barium in drinking water and human samples. This study showed significant correlations between levels of arsenic and barium, but not its homologous elements (magnesium, calcium and strontium), in urine, toenail and hair samples obtained from residents of Jessore, Bangladesh. Significant correlation between levels of arsenic and barium in well drinking water and levels in human urine, toenail and hair samples were also observed. Based on these results, a high-performance and low-cost adsorbent composed of a hydrotalcite-like compound for barium and arsenic was developed. The adsorbent reduced levels of barium and arsenic from well water in Bangladesh and Vietnam to <7 µg/L within 1 min. Thus, we have showed levels of arsenic and barium in humans and propose a novel remediation system. 相似文献
79.
Yasuhiro Umemura Junko Yoshida Masashi Wada Yoshiki Tsuchiya Yoichi Minami Hitomi Watanabe Gen Kondoh Junji Takeda Hitoshi Inokawa Kyoji Horie Kazuhiro Yagita 《PloS one》2013,8(6)
We previously reported emergence and disappearance of circadian molecular oscillations during differentiation of mouse embryonic stem (ES) cells and reprogramming of differentiated cells, respectively. Here we present a robust and stringent in vitro circadian clock formation assay that recapitulates in vivo circadian phenotypes. This assay system first confirmed that a mutant ES cell line lacking Casein Kinase I delta (CKIδ) induced ∼3 hours longer period-length of circadian rhythm than the wild type, which was compatible with recently reported results using CKIδ null mice. In addition, this assay system also revealed that a Casein Kinase 2 alpha subunit (CK2α) homozygous mutant ES cell line developed significantly longer (about 2.5 hours) periods of circadian clock oscillations after in vitro or in vivo differentiation. Moreover, revertant ES cell lines in which mutagenic vector sequences were deleted showed nearly wild type periods after differentiation, indicating that the abnormal circadian period of the mutant ES cell line originated from the mutation in the CK2α gene. Since CK2α deficient mice are embryonic lethal, this in vitro assay system represents the genetic evidence showing an essential role of CK2α in the mammalian circadian clock. This assay was successfully applied for the phenotype analysis of homozygous mutant ES cells, demonstrating that an ES cell-based in vitro assay is available for circadian genetic screening. 相似文献
80.