全文获取类型
收费全文 | 624篇 |
免费 | 28篇 |
国内免费 | 6篇 |
专业分类
耳鼻咽喉 | 3篇 |
儿科学 | 6篇 |
妇产科学 | 4篇 |
基础医学 | 83篇 |
口腔科学 | 9篇 |
临床医学 | 51篇 |
内科学 | 166篇 |
皮肤病学 | 9篇 |
神经病学 | 47篇 |
特种医学 | 19篇 |
外科学 | 101篇 |
综合类 | 4篇 |
预防医学 | 19篇 |
眼科学 | 5篇 |
药学 | 77篇 |
中国医学 | 3篇 |
肿瘤学 | 52篇 |
出版年
2023年 | 5篇 |
2022年 | 11篇 |
2021年 | 12篇 |
2020年 | 5篇 |
2019年 | 5篇 |
2018年 | 9篇 |
2017年 | 2篇 |
2016年 | 18篇 |
2015年 | 13篇 |
2014年 | 13篇 |
2013年 | 21篇 |
2012年 | 26篇 |
2011年 | 50篇 |
2010年 | 27篇 |
2009年 | 21篇 |
2008年 | 38篇 |
2007年 | 51篇 |
2006年 | 66篇 |
2005年 | 49篇 |
2004年 | 49篇 |
2003年 | 41篇 |
2002年 | 46篇 |
2001年 | 9篇 |
2000年 | 7篇 |
1999年 | 7篇 |
1998年 | 12篇 |
1997年 | 5篇 |
1996年 | 4篇 |
1995年 | 4篇 |
1994年 | 4篇 |
1993年 | 1篇 |
1992年 | 5篇 |
1991年 | 6篇 |
1990年 | 1篇 |
1989年 | 2篇 |
1988年 | 5篇 |
1986年 | 1篇 |
1985年 | 1篇 |
1983年 | 1篇 |
1980年 | 1篇 |
1978年 | 1篇 |
1975年 | 1篇 |
1968年 | 2篇 |
排序方式: 共有658条查询结果,搜索用时 15 毫秒
11.
Megumi Ueno Ikuo Nakanishi Ken-ichiro Matsumoto 《Journal of Clinical Biochemistry and Nutrition》2013,52(2):95-100
A method for correctly assessing hydroxyl radical scavenging activity of antioxidative chemicals and/or biological compounds/materials was proposed. This method can simultaneously assess two factors, i.e. hydroxyl radical-scavenging and 5,5-dimethyl-2-hydroxy-1-pyrrolidine-N-oxide (hydroxyl radical adduct of 5,5-dimethyl-1-pyrroline-N-oxide)-reducing ability, as antioxidative properties. In this paper, some biologically common hydrophilic molecules, cell culture media, and rat plasma were tested. X-ray-induced hydroxyl radical can be detected using the electron paramagnetic resonance spin trapping technique. Using X-ray irradiation of the reaction mixture as the hydroxyl radical source, the true hydroxyl radical-scavenging ability of the subjected antioxidant can be assessed. In addition, the method simultaneously measures the reduction of 5,5-dimethyl-2-hydroxy-1-pyrrolidine-N-oxide, to estimate the reducing ability of the antioxidant. Biological materials, such as sugars and proteins, could abolish hydroxyl radical at the biological concentration. Ascorbic acid showed reducing ability at the biological concentration. The simultaneous assessment of hydroxyl radical-scavenging and reducing ability of antioxidants can be an informative index for antioxidants. 相似文献
12.
Emiko Sekine-Suzuki Ikuo Nakanishi Kohei Imai Megumi Ueno Takashi Shimokawa Ken-ichiro Matsumoto Kiyoshi Fukuhara 《RSC advances》2018,8(19):10158
About two thirds of biological damage due to low linear energy transfer (LET) radiation, such as X-rays and the plateau region of heavy-ion beams, is known to be caused by the hydroxyl radical (˙OH), the most powerful reactive oxygen species (ROS), generated via ionisation and excitation of water molecules. Thus, compounds having an efficient scavenging activity against ROS are expected to exhibit a radioprotective activity. A planar catechin analogue, where an isopropyl fragment was introduced into the catechol ring of (+)-catechin, showed an efficient protective effect against X-ray induced apoptosis in rat thymocytes compared to (+)-catechin. The planar catechin scavenged 2,2-diphenyl-1-picrylhydrazyl radicals (DPPH˙) solubilised in water by β-cyclodextrin about 10-fold faster than (+)-catechin in phosphate buffer (0.1 M, pH 7.4) at 298 K. Furthermore, the experimental log P value of the planar catechin (1.22) is reported to be significantly larger than that of (+)-catechin (0.44). The higher radical-scavenging activity and lipophilicity of the planar catechin than those of (+)-catechin may contribute in part to the higher protective activity against X-ray-induced apoptosis in rat thymocytes.A planar catechin analogue showed a significant higher protective activity against X-ray induced apoptosis in rat thymocytes than (+)-catechin. 相似文献
13.
Morimasa Sekiguchi Yuzo Fujii Atsuko Saito Toshimitsu Suzuki Yasuko Shiroko Hisayoshi Nakamura Ken-ichiro Hasumi 《Journal of gastroenterology》1995,30(5):589-598
We describe a gastric carcinoma cell line that has been maintained in vitro for more than 10 years and retains the capacity
to produce a large amount of alpha-fetoprotein. This cell line was isolated from a metastatic lymph node of a 63-year-old
male patient with advanced gastric carcinoma (T2N3P0H0M0) who showed high serum levels of alpha-fetoprotein. The primary tumor
was moderately differentiated tubular adenocarcinoma and the lymph node was poorly differentiated adenocarcinoma without any
particular pattern. The cultured cells grew as densely packed islet-like colonies with small polygonal cells. Electron microscopy
revealed cells abundant in cytoplasmic organelles, with some cellular attachments being tight with junctional complexes and
some being loose across intercellular spaces. The free cell surface had microvilli. The population doubling-time was 152 h
at passage 58. Chromosomal analysis revealed the modal number to be 77, with numerous karyotype abnormalities. The tumorigenicity
of the cultured cells in athymic nude mice was positive only when they were subcutaneously transplanted beneath a plastic
plate, but when the cells were transplanted subcutaneously or administered by intrasplenic injection in intact or weakly irradiated
nude mice, no tumorigenicty was shown. The cell line produced tumor-associated antigens, such as alpha-fetoprotein, carcinoembryonic
antigen, and tissue polypeptide antigen. This cell line may be useful for comparative studies of different types of gastric
carcinoma and alpha-fetoproteins of different origins. 相似文献
14.
An optimal therapeutic expression level is crucial for suicide gene therapy for hepatic metastatic cancer in mice 总被引:5,自引:0,他引:5
Terazaki Y Yano S Yuge K Nagano S Fukunaga M Guo ZS Komiya S Shirouzu K Kosai K 《Hepatology (Baltimore, Md.)》2003,37(1):155-163
The most serious problem in current gene therapy is discrepancies between experimental data and actual clinical outcomes, which may be due to insufficient analyses and/or inappropriate animal models. We have explored suicide gene therapy by using various clinically relevant animal models and doubt the clinical use of maximal suicide gene expression, which has been generally recommended. To explore this subject further, we studied what expression level of suicide gene and what promoter led to the maximal clinical benefit in the case of hepatic metastatic cancer in mice. Therapeutic and adverse side effects of 4 adenoviral vectors that express herpes simplex virus thymidine kinase (HSV-tk) under different promoters were scrupulously investigated in 2 mouse models of hepatic metastasis of gastric cancer that possess clinical characteristics. Surprisingly, increases in HSV-tk expression beyond a certain point, achieved by the Rous sarcoma virus long terminal repeat promoter, not only enhanced the adverse side effects of lethal hepatotoxicity and ganciclovir-independent cytotoxicity but also failed to further increase therapeutic potential. Moreover, the carcinoembryonic antigen (CEA) tumor-specific promoter, the therapeutic potential of which had been underestimated, was much more useful-even in the case of low CEA-producing cancer-than had been previously reported. In conclusion, the optimal therapeutic expression level of a suicide gene is a novel concept and a crucial factor for successful cancer gene therapy. The present results, which contradict those of previous studies, alert researchers about possible problems with ongoing and future clinical trials that lack this concept. 相似文献
15.
Nishida K Doita M Takada T Shimomura T Maeno K Kakutani K Miyamoto H Kurosaka M 《Clinical calcium》2005,15(3):79-86
Intervertebral disc degeneration and associated spinal disorders including low back pain are a leading source of morbidity and a major cause of work disability as well as increased health care costs. Recent advance of molecular biology enable us to utilize these new techniques for understanding disc cell function and mechanisms of disc degeneration. Furthermore, these new technology may open novel therapeutic strategy such as application of growth factors, stem cell therapy, and gene therapy to regenerate degenerated intervertebral discs. 相似文献
16.
Hiroko P. Indo Hsiu-Chuan Yen Ikuo Nakanishi Ken-ichiro Matsumoto Masato Tamura Yumiko Nagano Hirofumi Matsui Oleg Gusev Richard Cornette Takashi Okuda Yukiko Minamiyama Hiroshi Ichikawa Shigeaki Suenaga Misato Oki Tsuyoshi Sato Toshihiko Ozawa Daret K. St. Clair Hideyuki J. Majima 《Journal of Clinical Biochemistry and Nutrition》2015,56(1):1-7
Fridovich identified CuZnSOD in 1969 and manganese superoxide dismutase (MnSOD) in 1973, and proposed ”the Superoxide Theory,” which postulates that superoxide (O2•−) is the origin of most reactive oxygen species (ROS) and that it undergoes a chain reaction in a cell, playing a central role in the ROS producing system. Increased oxidative stress on an organism causes damage to cells, the smallest constituent unit of an organism, which can lead to the onset of a variety of chronic diseases, such as Alzheimer’s, Parkinson’s, amyotrophic lateral sclerosis and other neurological diseases caused by abnormalities in biological defenses or increased intracellular reactive oxygen levels. Oxidative stress also plays a role in aging. Antioxidant systems, including non-enzyme low-molecular-weight antioxidants (such as, vitamins A, C and E, polyphenols, glutathione, and coenzyme Q10) and antioxidant enzymes, fight against oxidants in cells. Superoxide is considered to be a major factor in oxidant toxicity, and mitochondrial MnSOD enzymes constitute an essential defense against superoxide. Mitochondria are the major source of superoxide. The reaction of superoxide generated from mitochondria with nitric oxide is faster than SOD catalyzed reaction, and produces peroxynitrite. Thus, based on research conducted after Fridovich’s seminal studies, we now propose a modified superoxide theory; i.e., superoxide is the origin of reactive oxygen and nitrogen species (RONS) and, as such, causes various redox related diseases and aging. 相似文献
17.
Minatoguchi S Takemura G Chen XH Wang N Uno Y Koda M Arai M Misao Y Lu C Suzuki K Goto K Komada A Takahashi T Kosai K Fujiwara T Fujiwara H 《Circulation》2004,109(21):2572-2580
18.
Matsuda I Nakamaki T Amaya H Kiyosaki M Kawakami K Yamada K Yokoyama A Hino K Tomoyasu S 《[Rinshō ketsueki] The Japanese journal of clinical hematology》2003,44(9):946-951
A 22-year-old female was diagnosed as having acute lymphoid leukemia (ALL) in February 1995, from the findings of peroxidase negative, CD10+, CD19+, TdT+ and rearrangement of IgH and TCR beta. AdVP (doxorubicin, vincristine and prednisolone) therapy achieved a complete remission (CR). Bone marrow transplantation had to be abandoned because of the lack of an HLA-identical donor. Intensification therapy was thus carried out repeatedly. In June 1998, myeloblast with Auer rods, peroxidase positive, CD13+, CD33+ and HLA-DR+, appeared. The patient was diagnosed as having lineage switch acute myeloid leukemia (AML) from ALL. Though A-DMP (cytosine arabinoside, daunorubicin, 6-mercaptopurine) therapy was resistant, AdVP therapy led to a CR. The patient died of cardiotoxicity from anthracyclines in February 1999. From the results of the Ramasamy method using the clonal rearrangements of the Ig heavy chain gene locus, the origin of the pathological cells of ALL and AML was indicated to be the same leukemia clone. 相似文献
19.
20.
Junling Yang Abhinandan Pattanayak Min Song Jinghong Kou Hiroaki Taguchi Sudhir Paul Selvarangan Ponnazhagan Robert Lalonde Ken-ichiro Fukuchi 《Journal of molecular neuroscience : MN》2013,49(2):277-288
We previously reported that anti-amyloid-beta (Aβ) single-chain antibody (scFv59) brain delivery via recombinant adeno-associated virus (rAAV) was effective in reducing cerebral Aβ load in an Alzheimer’s disease (AD) mouse model without inducing inflammation. Here, we investigated the prophylactic effects and mechanism of a muscle-directed gene therapy modality in an AD mouse model. We injected rAAV serotype 1 encoding scFv59 into the right thigh muscles of 3-month-old mice. Nine months later, high levels of scFv59 expression were confirmed in the thigh muscles by both immunoblotting and immunohistochemistry. As controls, model mice were similarly injected with rAAV1 encoding antihuman immunodeficiency virus Gag antibody (scFvGag). AAV1-mediated scFv59 gene delivery was effective in decreasing Aβ deposits in the brain. Compared with the scFvGag group, levels of Aβ in cerebrospinal fluid (CSF) decreased significantly while Aβ in serum tended to increase in the scFv59 group. AAV1-mediated scFv59 gene delivery may alter the equilibrium of Aβ between the blood and brain, resulting in an increased efflux of Aβ from the brain owing to antibody-mediated sequestration/clearance of peripheral Aβ. Our results suggest that muscle-directed scFv59 delivery via rAAV1 may be a prophylactic option for AD and that levels of CSF Aβ may be used to evaluate the efficacy of anti-Aβ immunotherapy. 相似文献