全文获取类型
收费全文 | 3852篇 |
免费 | 296篇 |
国内免费 | 31篇 |
学科分类
医药卫生 | 4179篇 |
出版年
2023年 | 37篇 |
2022年 | 30篇 |
2021年 | 178篇 |
2020年 | 106篇 |
2019年 | 131篇 |
2018年 | 151篇 |
2017年 | 112篇 |
2016年 | 108篇 |
2015年 | 145篇 |
2014年 | 157篇 |
2013年 | 182篇 |
2012年 | 285篇 |
2011年 | 269篇 |
2010年 | 169篇 |
2009年 | 132篇 |
2008年 | 255篇 |
2007年 | 230篇 |
2006年 | 230篇 |
2005年 | 238篇 |
2004年 | 214篇 |
2003年 | 200篇 |
2002年 | 161篇 |
2001年 | 50篇 |
2000年 | 54篇 |
1999年 | 53篇 |
1998年 | 36篇 |
1997年 | 31篇 |
1996年 | 15篇 |
1995年 | 18篇 |
1994年 | 13篇 |
1993年 | 9篇 |
1992年 | 16篇 |
1991年 | 14篇 |
1990年 | 14篇 |
1989年 | 23篇 |
1988年 | 4篇 |
1987年 | 13篇 |
1986年 | 10篇 |
1985年 | 6篇 |
1984年 | 10篇 |
1983年 | 9篇 |
1982年 | 4篇 |
1981年 | 7篇 |
1980年 | 4篇 |
1979年 | 7篇 |
1978年 | 8篇 |
1974年 | 5篇 |
1971年 | 5篇 |
1970年 | 6篇 |
1967年 | 3篇 |
排序方式: 共有4179条查询结果,搜索用时 15 毫秒
1.
2.
Nobuhiko Joki Hiroki Hase Yuri Tanaka Yasunori Takahashi Tomokatsu Saijyo Hiroyaou Ishikawa Yoji Inishi Yoshihiko Imamura Hisao Hara Taro Tsunoda Masato Nakamura 《Nephrology, dialysis, transplantation》2006,21(6):1633-1639
BACKGROUND: In patients with chronic kidney disease (CKD), although strong associations have been observed between malnutrition and atherosclerosis, the relationship between serum albumin concentration and angiographic changes of coronary artery disease (CAD) remains poorly explored. The goal of the present study was, in patients with CKD, to clarify the relationship between the angiographic severity of CAD and serum albumin concentration reflecting either inflammation or nutrition or both. METHODS: In this study, 100 end-stage renal disease (ESRD) patients were enrolled, who commenced long-term dialysis therapy at our hospital and underwent coronary angiography within 3 months of the first haemodialysis (HD) session. Mean age was 63+/-11 years, 20% of the subjects were female and 62% had diabetes. Severity of CAD was evaluated in terms of (i) number of vessels exhibiting CAD (>or=75% stenosis) and (ii) Gensini score (GS). Clinical characteristics and laboratory findings were recorded at initiation of long-term HD therapy. We then evaluated a possible association with the presence and degree of CAD. RESULTS: Sixty-four patients exhibited signs of CAD. Forty-one among them (64%) had multivessel disease. On univariate logistic regression analysis, age, diabetes and hypoalbuminaemia were significantly associated with multivessel CAD. Univariate linear regression analysis demonstrated a positive correlation of age and diabetes with GS, and an inverse correlation of BMI and serum albumin level with GS. Stepwise regression analysis showed age and serum albumin level to be independently associated with multivessel CAD and GS. The ROC curves demonstrated best cut-off levels of age and albumin for predicting multivessel CAD to be 70 years and 3.15 g/dl, respectively. CONCLUSION: Hypoalbuminaemia at the initiation of dialysis is an important predictor of advanced CAD, particularly in male and in diabetic patients. It may reflect mainly a state of inflammation. However, malnutrition as a confounding factor cannot be entirely excluded. 相似文献
3.
Changes in central dopaminergic systems with the expression of Shh or GDNF in mice perinatally exposed to bisphenol-A. 总被引:1,自引:0,他引:1
Kazuya Miyagawa Minoru Narita Michiko Narita Keiichi Niikura Hisahiko Akama Yuri Tsurukawa Tsutomu Suzuki 《Nihon shinkei seishin yakurigaku zasshi》2007,27(2):69-75
In the previous study, we reported that exposure to bisphenol-A induced the potentiation of dopamine receptor functions in the mouse limbic area, resulting in supersensitivity to methamphetamine-induced pharmacological actions. The present study was undertaken to investigate whether prenatal exposure to bisphenol-A could produce morphological change in dopaminergic neuron and the pattern of expression of genes regulating the dopaminergic neuron development. Here we found that prenatal and neonatal exposures to bisphenol-A increased the tyrosine hydroxylase- and dopamine transporter-like immunoreactivities in the adult mouse limbic area. The present molecular biological study shows that chronic bisphenol-A treatment produced a significant decrease in the dopaminergic neuron development factors, sonic hedgehog and glial cell line-derived neurotrophic factor, which were also decreased by prenatal exposure to bisphenol-A. These results suggest that chronic exposure to bisphenol-A could disrupt the dopaminergic neurotransmission in the process of dopaminergic neuron development. 相似文献
4.
5.
Tatsuya Okimoto Hiroshi Yahata Yasuhiko Fukuda Keisuke Hayamizu Kiyohiko Dohi 《Transplant international》1994,7(S1):629-633
Abstract A study was conducted to elucidate the mechanism of donor-pecific Mixed Lymphocyte Reaction (MLR and Cell Mediated Lymphotoxicity (CML) unresponsiveness in a renal transplant recipient with a long-term well-functioning kidney. The peripheral blood lymphocytes (PBL) of the recipient, who had not shown rejection since his transplantation 5 years previously, and those of his mother (donor), his father and two healthy third parties were examined. MLR, CML, semimicro MLR in a double chamber, interleukin-2 (IL-2) synthesis assay and limiting dilution assay were performed. This recipient showed donor-pecific MLR and CML unresponsiveness. IL-2 assay showed that the PBL of the recipient produced less IL-2 against the donor than against the father and the third parties. The addition of exogenous recombinant IL-2 (rIL-2; Takeda Co.) to the priming MLR caused a recovery of CML against the donor. A limiting dilution assay indicated that cytotoxic T cell precursor (CTLp) frequencies against the donor and father did not differ. The suppressor assay in a double chamber indicated that the PBL of the recipient stimulated by the donor PBL had a non-pecific suppressive effect on MLR, CML and IL-2 synthesis of the PBL across the Major Histocompatibility Complex (MHC) barrier. This suppressive effect was abolished by OKT3 or OKT8 monoclonal antibody and complement. Thus, the recipient had donor-pecific suppressor T cells that produced a humoral non-pecific suppressive factor only when stimulated by the donor PBL, and this factor suppressed PLR and CML by inhibiting IL-2 synthesis of the PBL. 相似文献
6.
Role of macrophage and smooth muscle cell apoptosis in association with oxidized low-density lipoprotein in the atherosclerotic development. 总被引:5,自引:0,他引:5
Yuri Akishima Yoshikiyo Akasaka Yukio Ishikawa Zhang Lijun Hideko Kiguchi Kinji Ito Hiroyuki Itabe Toshiharu Ishii 《Modern pathology》2005,18(3):365-373
To examine the role of the apoptosis of macrophages and smooth muscle cells in the development of atherosclerosis, human aortic tissues with intimal lesions were immunostained with antibodies against terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL), single-stranded DNA (clone F7-26), and active caspase-3. Apoptotic cells were detected in the intima using both TUNEL and single-stranded DNA, however, the latter method was the more sensitive one for detecting apoptotic cells in the early stages of atherosclerosis. The number of apoptotic cells increased as the disease progressed. It implies that the apoptosis of intimal cells is involved in the formation of atherosclerotic lesions. In addition, quantitative analyses of the cell types undergoing apoptosis using double-immunostaining revealed that the susceptibility of macrophages and smooth muscle cells to apoptosis was greater specifically in atheroma than in the other atherosclerotic lesions, and macrophages were more susceptible to apoptosis than smooth muscle cells. The frequency and spatial distribution of oxidized low-density lipoprotein (oxLDL) (FOH1a/DLH3)-positive cells were examined by immunohistochemistry, and the results resembled those of apoptotic cells. The number of oxLDL-positive cells in the intima significantly correlated with the susceptibility of smooth muscle cells, but not with that of macrophages, to apoptosis. These results suggest that oxLDL affects the apoptosis of smooth muscle cells during the atherosclerotic development. 相似文献
7.
Toshiharu Mori Nobukazu Okimoto Akinori Sakai Yuichi Okazaki Nariaki Nakura Takuya Notomi Toshitaka Nakamura 《Journal of bone and mineral research》2003,18(11):2002-2009
To investigate the relationship between the effects of bone turnover and bone marrow cell development in bone cells, we developed a mouse voluntary climbing exercise model. Climbing exercise increased bone volume and transient osteogenic potential of bone marrow. This model would be suitable for investigating the mechanistic roles of mechanical loading. INTRODUCTION: The relationship between bone mass gain and local bone formation and resorption in mechanically loaded bone is not well understood. MATERIALS AND METHODS: Sixty-five C57BL/6J mice, 8 weeks of age, were assigned to five groups: a baseline control and two groups each of ground control and climbing exercise mice for 2 and 4 weeks. Mice were housed in a 100-cm tower and had to climb toward a bottle placed at the top to drink water. RESULTS: Compared with the ground control, bone mineral density of the left femur increased in the climbing mice at 4 weeks. At 2 and 4 weeks, bone formation rate (BFR/BS) of periosteal surface, the cross-sectional area, and moment of inertia were increased in the climbing mice, whereas BFR/BS and eroded surface (ES/BS) of endosteal surface did not differ. The trabecular bone volume (BV/TV) of the proximal tibia increased in climbing mice, and osteoclast surface (Oc.S/BS) and osteoclast number decreased at 2 weeks. At 4 weeks, there were increases in BV/TV and parameters of bone formation, including mineralized surface, mineral apposition rate, and bone formation rate. In marrow cell cultures from the tibia, the number of alkaline phosphatase+ colony forming units-fibroblastic and the area of mineralized nodule formation in climbing mice were increased, and the number of osteoclast-like TRACP+ multinucleated cells was lower at 2 weeks. At 4 weeks, these parameters recovered to the levels of the ground controls. CONCLUSION: Our results indicate that climbing increased trabecular bone volume and reduced bone resorption, with a subsequent increase in bone formation. Intermittent climbing downregulates marrow osteoclastogenic cells and upregulates osteogenic cells initially, but further exercise seemed to desensitize them. Cortical envelopes were enlarged earlier, but the response seems to differ from trabecular bone. 相似文献
8.
9.
Yoshikiyo Akasaka MD PhD ; Kinji Ito PhD ; Kazuko Fujita PhD ; Kazuo Komiyama DDS ; Ichiro Ono MD PhD ; Yukio Ishikawa MD PhD ; Yuri Akishima MD PhD ; Hiroko Sato MD PhD ; Toshiharu Ishii MD PhD 《Wound repair and regeneration》2005,13(4):373-382
To characterize apoptosis in keloids and the mechanisms responsible for this process, the expression of activated caspase-9 and -3 in fibroblasts obtained from keloids was analyzed. Immunohistochemistry revealed that the number of fibroblasts positive for terminal deoxynucleotide transferase-mediated dUTP nick-end labeling (TUNEL) or activated caspase-9 or -3 was low but was significantly higher in keloid tissues than in normal scar tissues. Significant relationships between the number of caspase-positive fibroblasts and TUNEL-positive fibroblasts suggested that the activation of caspase-9 and -3 induces apoptosis in a subpopulation of keloid fibroblasts. All keloid fibroblast cell lines established in this study showed activation of caspase-9 and -3 after serum deprivation for 3 or 4 hours, as shown using Western blotting. Furthermore, serum deprivation-induced apoptosis in a keloid fibroblast line was blocked by a caspase-9 inhibitor (acetyl-Leu-Glu-His-Asp-al), indicating that activation of caspase-9 was necessary for the process of apoptosis in keloid fibroblasts. Although serum deprivation did not significantly change the level of apoptosis protease activating factor-1 in any of the lines, cytochrome c release was detected in cytosolic fractions of the lines after serum deprivation for 3 or 4 hours. These results strongly suggest that keloid fibroblasts are predisposed to apoptosis and cytochrome c release and that caspase-9 activation may underlie regulation of apoptosis in keloid fibroblasts in vivo. 相似文献
10.
Yuri P Zverev Humphrey E Misiri 《Malawi medical journal : the journal of Medical Association of Malawi》2009,21(1):19-21
The aim of this longitudinal study was to assess the effect of rotating shift work on perceived sleep quality and sleep duration of nurses at Queen Elizabeth Central Hospital, Blantyre, Malawi. Twenty four female nurses were recruited at random from among personnel engaged in rotating shift work. The nurses worked a three-phase schedule: five day shifts (7.00 – 17.00) followed by three night shifts (17.00 – 7.00) and five days off. Controls were 22 female nurses who did not perform night duties. Sleep quality and duration was assessed using standardized and validated questionnaires on sleep duration and subjective sleep quality (SSQ). One-way analysis of variance revealed a significant effect of shift phase on total sleep duration (F = 36.8, d.f. = 8, P < 0.000) and perceived sleep quality (F = 8.81, d.f. = 3, P < 0.000). Night shift work was associated with reduction of sleep quality and duration. The after effects of night shifts persisted during days of the recovery period indicating accumulation of fatigue. 相似文献