全文获取类型
收费全文 | 2487篇 |
免费 | 139篇 |
国内免费 | 41篇 |
专业分类
耳鼻咽喉 | 8篇 |
儿科学 | 17篇 |
妇产科学 | 13篇 |
基础医学 | 291篇 |
口腔科学 | 25篇 |
临床医学 | 139篇 |
内科学 | 889篇 |
皮肤病学 | 61篇 |
神经病学 | 145篇 |
特种医学 | 101篇 |
外科学 | 399篇 |
综合类 | 2篇 |
预防医学 | 32篇 |
眼科学 | 61篇 |
药学 | 162篇 |
中国医学 | 16篇 |
肿瘤学 | 306篇 |
出版年
2023年 | 19篇 |
2022年 | 17篇 |
2021年 | 47篇 |
2020年 | 40篇 |
2019年 | 64篇 |
2018年 | 64篇 |
2017年 | 61篇 |
2016年 | 67篇 |
2015年 | 63篇 |
2014年 | 80篇 |
2013年 | 99篇 |
2012年 | 151篇 |
2011年 | 155篇 |
2010年 | 111篇 |
2009年 | 84篇 |
2008年 | 165篇 |
2007年 | 147篇 |
2006年 | 176篇 |
2005年 | 181篇 |
2004年 | 158篇 |
2003年 | 139篇 |
2002年 | 136篇 |
2001年 | 30篇 |
2000年 | 31篇 |
1999年 | 38篇 |
1998年 | 31篇 |
1997年 | 34篇 |
1996年 | 33篇 |
1995年 | 19篇 |
1994年 | 25篇 |
1993年 | 26篇 |
1992年 | 28篇 |
1991年 | 32篇 |
1990年 | 26篇 |
1989年 | 18篇 |
1988年 | 11篇 |
1987年 | 6篇 |
1986年 | 9篇 |
1985年 | 4篇 |
1984年 | 8篇 |
1983年 | 5篇 |
1982年 | 4篇 |
1981年 | 7篇 |
1980年 | 3篇 |
1979年 | 3篇 |
1978年 | 4篇 |
1975年 | 2篇 |
1974年 | 2篇 |
1970年 | 1篇 |
1964年 | 1篇 |
排序方式: 共有2667条查询结果,搜索用时 31 毫秒
41.
Regulation of p27 by S-phase kinase-associated protein 2 is associated with aggressiveness in non-small-cell lung cancer. 总被引:13,自引:0,他引:13
Atsushi Osoegawa Ichiro Yoshino Shinji Tanaka Kenji Sugio Toshifumi Kameyama Masafumi Yamaguchi Yoshihiko Maehara 《Journal of clinical oncology》2004,22(20):4165-4173
PURPOSE: The F-box protein S-phase kinase-associated protein 2 (Skp2) is one of the positive regulators of the cell cycle that promote ubiquitin-mediated proteolysis of the cyclin-dependent kinase inhibitor p27. In this study, we investigated the significance of Skp2 expression in human non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Clinicopathologic features and immunohistochemical expression of Skp2 and p27 proteins were studied in 138 patients with NSCLC. Survival analyses were performed using the Kaplan-Meier method and the Cox regression model. To analyze the role of Skp2 in vitro, NSCLC cells were transfected with an Skp2-expressing vector or small interfering RNA. RESULTS: Skp2 was overexpressed in males, smokers, patients with squamous cell carcinomas, and patients with poorly differentiated cancers (P = .034, < .0001, < .0001, and .002, respectively). The multivariant analysis revealed that Skp2 expression is an independent prognostic factor for survival in NSCLC. An inverse relationship of Skp2 with p27 expression was observed (P = .012), and patients with both a higher expression of Skp2 and a lower expression of p27 showed a significantly unfavorable prognosis (P = .0002). In vitro ectopic expression of Skp2 in NSCLC cells reduced the protein level of p27. Conversely, induction of Skp2 siRNA increased the protein level of p27, leading to growth inhibition in NSCLC cells. CONCLUSION: Skp2 overexpression is closely associated with the suppression of p27 and the aggressiveness in NSCLC. It also could be a therapeutic target in NSCLC. 相似文献
42.
Toshifumi Ozaki Silke Flege Matthias Kevric Norbert Lindner Rainer Maas Günter Delling Rudolf Schwarz Arthur R von Hochstetter Mechthild Salzer-Kuntschik Wolfgang E Berdel Heribert Jürgens G Ulrich Exner Peter Reichardt Regine Mayer-Steinacker Volker Ewerbeck Rainer Kotz Winfried Winkelmann Stefan S Bielack 《Journal of clinical oncology》2003,21(2):334-341
PURPOSE: To define patients and tumor characteristics as well as therapy results, patients with pelvic osteosarcoma who were registered in the Cooperative Osteosarcoma Study Group (COSS) were analyzed. PATIENTS AND METHODS: Sixty-seven patients with a high-grade pelvic osteosarcoma were eligible for this analysis. Fifteen patients had primary metastases. All patients received chemotherapy according to COSS protocols. Thirty-eight patients underwent limb-sparing surgery, 12 patients underwent hemipelvectomy, and 17 patients did not undergo definitive surgery. Eleven patients received irradiation to the primary tumor site: four postoperatively and seven as the only form of local therapy. RESULTS: Local failure occurred in 47 of all 67 patients (70%) and in 31 of 50 patients (62%) who underwent definitive surgery. Five-year overall survival (OS) and progression-free survival rates were 27% and 19%, respectively. Large tumor size (P =.0137), primary metastases (P =.0001), and no or intralesional surgery (P <.0001) were poor prognostic factors. In 30 patients with no or intralesional surgery, 11 patients with radiotherapy had better OS than 19 patients without radiotherapy (P =.0033). Among the variables, primary metastasis, large tumor, no or intralesional surgery, no radiotherapy, existence of primary metastasis (relative risk [RR] = 3.456; P =.0009), surgical margin (intralesional or no surgical excision; RR = 5.619; P <.0001), and no radiotherapy (RR = 4.196; P =.0059) were independent poor prognostic factors. CONCLUSION: An operative approach with wide or marginal margins improves local control and OS. If the surgical margin is intralesional or excision is impossible, additional radiotherapy has a positive influence on prognosis. 相似文献
43.
Osamu Miyamoto Takehiro Nakamura Shin-ich Yamagami Tetsuro Negi Masaaki Tokuda Hideki Matsui Toshifumi Itano 《Brain research》2000,873(1):418
To investigate the mechanism of chronic cell death following postischemic hypothermia, the change of N-methyl-
-aspartate receptor (NMDAR) were examined by immunohistochemistry of NMDAR1 and long-term potentiation (LTP) in the CA1 subfield of the gerbil hippocampus. At 1 week following postischemic hypothermia (32°C×4 h), all CA1 neurons survived; however, immunoreactivity of NMDAR1 increased in neuronal perikarya whereas decreased in dendrites in the CA1 neurons. The abnormality was still observed in remaining CA1 neurons at 1 month after hypothermia. LTP was also significantly depressed at 1 week after hypothermia. These results suggest that some abnormalities in the glutamate receptor may be caused by ischemia; such abnormality would persist in spite of hypothermia treatment, resulting in the depression of LTP. 相似文献
44.
Rie Fukui Eriko Tanabe Misaho Kitayoshi Kyohei Yoshikawa Nobuyuki Fukushima Toshifumi Tsujiuchi 《Tumour biology》2012,33(6):1899-1905
Lysophosphatidic acid (LPA) mediates a wide range of biological responses with G protein-coupled transmembrane receptors (LPA receptors). So far, at least six types of LPA receptors (LPA receptor-1 (LPA1) to LPA6) have been identified. Recently, it has been reported that LPA3 indicates opposite effects on cellular functions of cancer cells. In the present study, to assess a biological role of LPA3 on cell migration ability of colon cancer cells, we generated LPA receptor-3 (LPAR3) knockdown (HCT-sh3-3) cells from HCT116 and measured cell motile and invasion activities. In motility assay with a cell culture insert, HCT-sh3-3 cells showed significantly high cell motile activity, compared with control cells. For invasion assay, the filter was coated with Matrigel. The invasive activity of HCT-sh3-3 cells was significantly higher than that of control cells. Furthermore, we also examined the effects of LPAR3 knockdown on the interaction between colon cancer cells and endothelial F-2 cells. When F-2 cells were cultured with serum-free DMEM containing a supernatant from HCT-sh3-3 cells, the cell growth rate and migration activity of F-2 cells were significantly stimulated, associating with the elevated expressions of vascular endothelial growth factor (VEGF)-A and VEGF-C genes in HCT-sh3-3 cells. These results suggest that LPA3 may act as a negative regulator on cell motile and invasive abilities of colon cancer HCT116 cells. 相似文献
45.
Low‐dose etretinate shows promise in management of punctate palmoplantar keratoderma type 1: Case report and review of the published work
下载免费PDF全文
![点击此处可从《The Journal of dermatology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Toshifumi Nomura Reine Moriuchi Masae Takeda Shotaro Suzuki Kazuhiro Kikuchi Takamasa Ito Hiroshi Shimizu Satoko Shimizu 《The Journal of dermatology》2015,42(9):889-892
Punctate palmoplantar keratoderma type 1 (PPKP1) is a rare autosomal dominant disorder of keratinization, clinically characterized by punctate keratotic papules affecting the palmoplantar skin. Loss‐of‐function mutations in AAGAB have recently been reported as a cause of PPKP1. Despite the discovery of the genetic cause of PPKP1, pathogenesis‐based therapies are still unavailable. Moreover, little is known about the effectiveness of treatments for PPKP1. In this study, we analyzed a Japanese woman with PPKP1 and identified a novel frame‐shift mutation c.195_198del4 (p.Lys66Phefs*43) in AAGAB. Moreover, low‐dose etretinate was effective in improving the PPKP1 lesions in our patient. Our published work review identified only eight cases of PPKP1 with successful response to topical or systemic treatments. Notably, six of the cases were successfully treated with systemic retinoids. Thus, this study clearly provides further evidence that PPKP1 is caused by AAGAB mutations and that systemic retinoids are the most promising current treatment for PPKP1. 相似文献
46.
Mihoko Hatano Yoshihiro Matsumoto Jun-ichi Fukushi Tomoya Matsunobu Makoto Endo Seiji Okada Kunio Iura Satoshi Kamura Toshifumi Fujiwara Keiichiro Iida Yuko Fujiwara Akira Nabeshima Nobuhiko Yokoyama Suguru Fukushima Yoshinao Oda Yukihide Iwamoto 《Clinical & experimental metastasis》2015,32(6):579-591
47.
48.
Kosuke Nomura Toshiro Iizuka Daisuke Kaji Hisashi Yamamoto Yasutaka Kuribayashi Ryusuke Kimura Akihiro Yamada Tsukasa Furuhata Satoshi Yamashita Daisuke Kikuchi Akira Matsui Toshifumi Mitani Osamu Ogawa Shu Hoteya Yasunori Ota Shuichi Taniguchi Mitsuru Kaise 《Journal of gastroenterology and hepatology》2014,29(11):1867-1872
49.
Risa Konishi Ryota Tanaka Sae Inoue Yuki Ichimura Toshifumi Nomura Naoko Okiyama 《The Journal of dermatology》2022,49(1):118-123
Dermatomyositis, an idiopathic inflammatory myopathy, is characterized by cutaneous itchy manifestations, which are frequently refractory and recurrent even after intensive immunosuppressive treatments. To evaluate the effectiveness and safety of apremilast, an oral phosphodiesterase 4 inhibitor, in treating skin-dominant dermatomyositis in which myositis and interstitial lung disease are absent or in remission, we performed this prospective, single-arm, interventional study. A total of five Japanese patients (one male and four females, median [range] age, 64 [37–71] years) with refractory dermatomyositis-associated cutaneous manifestations were recruited and treated with a 12-week course of oral apremilast. Among five enrolled patients, three experienced diarrhea with full-dose apremilast (30 mg twice daily), two of whom withdrew from the study and recovered quickly afterwards. A total of three evaluable female patients (median [range] age, 65 [64–71] years) received apremilast treatment for 12 weeks. A 39.4% reduction from baseline Cutaneous Dermatomyositis Disease Area and Severity Index total activity score, but not the damage score, at week 12 was observed in all three patients. Visual analog scale of itching, and quality of life by Dermatology Life Quality Index were slightly improved in one and two apremilast-treated patients, respectively. As apremilast was effective, with expected and recoverable digestive adverse events (diarrhea), in patients with refractory and recurrent dermatomyositis-associated cutaneous manifestations in this first phase Ib study, it can be suggested as a possible treatment when aggressive immunosuppressive therapies with high-dose systemic corticosteroid and/or immunosuppressive agents for other manifestations, myositis, and interstitial lung disease, are not required. 相似文献
50.