全文获取类型
收费全文 | 746篇 |
免费 | 33篇 |
专业分类
779篇 |
出版年
2023年 | 1篇 |
2022年 | 6篇 |
2021年 | 4篇 |
2020年 | 4篇 |
2019年 | 4篇 |
2018年 | 5篇 |
2017年 | 13篇 |
2016年 | 9篇 |
2015年 | 24篇 |
2014年 | 39篇 |
2013年 | 42篇 |
2012年 | 77篇 |
2011年 | 43篇 |
2010年 | 36篇 |
2009年 | 34篇 |
2008年 | 54篇 |
2007年 | 48篇 |
2006年 | 61篇 |
2005年 | 56篇 |
2004年 | 43篇 |
2003年 | 54篇 |
2002年 | 44篇 |
2001年 | 10篇 |
2000年 | 4篇 |
1999年 | 7篇 |
1998年 | 7篇 |
1997年 | 6篇 |
1996年 | 7篇 |
1995年 | 8篇 |
1994年 | 2篇 |
1993年 | 5篇 |
1992年 | 4篇 |
1991年 | 1篇 |
1990年 | 1篇 |
1989年 | 1篇 |
1986年 | 1篇 |
1984年 | 2篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1981年 | 1篇 |
1979年 | 1篇 |
1978年 | 2篇 |
1977年 | 2篇 |
1975年 | 1篇 |
1974年 | 1篇 |
1973年 | 1篇 |
1972年 | 1篇 |
排序方式: 共有779条查询结果,搜索用时 0 毫秒
151.
Kouji Banno Megumi Yanokura Yusuke Kobayashi Makiko Kawaguchi Hiroyuki Nomura Akira Hirasawa Nobuyuki Susumu Daisuke Aoki 《Current Genomics》2009,10(2):127-132
Some cases of endometrial cancer are associated with a familial tumor and are referred to as hereditary nonpolyposis colorectal cancer (HNPCC or Lynch syndrome). Such tumors are thought to be induced by germline mutation of the DNA mismatch repair (MMR) gene, but many aspects of the pathology of familial endometrial cancer are unclear and no effective screening method has been established. However, the pathology of endometrial cancer with familial tumor has been progressively clarified in recent studies. At present, about 0.5% of all cases of endometrial cancers meet the clinical diagnostic criteria for HNPCC. A recent analysis of the three MMR genes (hMLH1, hMSH2 and hMSH6) revealed germline mutations in 18 of 120 cases (15.0%) of endometrial cancer with familial accumulation of cancer or double cancer, with a frameshift mutation of the hMSH6 gene being the most common. Many cases with mutation did not meet the current clinical diagnostic criteria for HNPCC, indicating that familial endometrial cancer is often not diagnosed as HNPCC. The results suggest that the hMSH6 gene mutation may be important in carcinogenesis in endometrial cancer and germline mutations of the MMR gene may be more prevalent in cases associated with familial accumulation of cancer. An international large-scale muticenter study is required to obtain further information about the pathology of endometrial cancer as a familial tumor.Key Words: HNPCC, Endometrial cancer, DNA mismatch repair gene, hMLH1, hMSH6. 相似文献
152.
Shinya Ohata Makiko Nawa Tokiwa Yamasaki Kenji Sawanobori Shoji Hata Yoichi Asaoka Hitoshi Okamoto Shuji Terai Toshiaki Katada 《Biochemical and biophysical research communications》2009,379(4):817-230
The fetal liver serves as the predominant hematopoietic organ until birth. However, the mechanisms underlying this link between hematopoiesis and hepatogenesis are unclear. Previously, we reported the isolation of a monoclonal antibody (anti-Liv8) that specifically recognizes an antigen (Liv8) present in murine fetal livers at embryonic day 11.5 (E11.5). Liv8 is a cell surface molecule expressed by hematopoietic cells in both fetal liver and adult mouse bone marrow. Here, we report that Liv8 is also transiently expressed by hepatoblasts at E11.5. Using protein purification and mass spectrometry, we have identified Liv8 as the CD44 protein. Interestingly, the expression of Liv8/CD44 in fetal liver was completely lost in AML1−/− murine embryos, which lack definitive hematopoiesis. These results show that hepatoblasts change from Liv8/CD44-negative to Liv8/CD44-positive status in a hematopoiesis-dependent manner by E11.5, and indicate that Liv8/CD44 expression is an important link between hematopoiesis and hepatogenesis during fetal liver development. 相似文献
153.
Makiko Suto Hidekazu Tanaka Yasuhide Mochizuki Jun Mukai Hiroki Takada Fumitaka Soga Kumiko Dokuni Yutaka Hatani Keiko Hatazawa Hiroki Matsuzoe Hiroyuki Sano Hiroyuki Shimoura Junichi Ooka Kensuke Matsumoto Yushi Hirota Wataru Ogawa Ken-ichi Hirata 《Cardiovascular diabetology》2017,16(1):145
Background
Coexistence of left ventricular (LV) longitudinal myocardial systolic dysfunction with LV diastolic dysfunction could lead to heart failure with preserved ejection fraction (HFpEF). Diabetes mellitus (DM) is known as a significant factor associated with HFpEF. Although the mechanisms of DM-related LV myocardial injury are complex, it has been postulated that overweight contributes to the development of LV myocardial injury in type 2 diabetes mellitus (T2DM) patients. However, the precise impact of overweight on LV longitudinal myocardial systolic function in T2DM patients remains unclear.Methods
We studied 145 asymptomatic T2DM patients with preserved LV ejection fraction (LVEF) without coronary artery disease. LV longitudinal myocardial systolic function was assessed by global longitudinal strain (GLS), which was defined as the average peak strain of 18-segments obtained from standard apical views. Overweight was defined as body mass index (BMI) ≥ 25 kg/m2. Ninety age-, gender- and LVEF-matched healthy volunteers served as controls.Results
GLS of overweight T2DM patients was significantly lower than that of non-overweight patients (17.9 ± 2.4% vs. 18.9 ± 2.6%, p < 0.05), whereas GLS of both overweight and non-overweight controls was similar (19.8 ± 1.3% vs. 20.4 ± 2.1%, p = 0.38). Furthermore, multiple regression analysis revealed that for T2DM patients, BMI was the independent determinant parameters for GLS as well as LV mass index.Conclusions
Overweight has a greater effect on LV longitudinal myocardial systolic function in T2DM patients than on that in non-DM healthy subjects. Our finding further suggests that the strict control of overweight in T2DM patients may be associated with prevention of the development of HFpEF.154.
155.
156.
Toyoizumi T Ohta R Nakagawa Y Tazura Y Kuwagata M Noguchi S Yamakage K 《Mutation research》2011,726(2):175-180
The aim of the present study was to evaluate both sensitivity and specificity of an in vivo skin comet assay using chemically treated, hairless mouse dorsal skin as a model. N-methyl-N'-nitro-N-nitrosoguanidine (MNNG, 0.0125-0.2%), 4-nitroquinoline-1-oxide (4NQO, 0.01-0.25%), mitomycin C (MMC, 0.0125-0.05%), benzo[a]pyrene (B[a]P, 0.25-2%), and 7,12-dimethylbenz[a]anthracene (DMBA, 0.25-1%) were each applied once to the dorsal skin of hairless male mice; after 3h, epidermal skin cells were isolated, and the alkaline comet assay was performed. The assay was performed after 24h for only the B[a]P and DMBA. Furthermore, B[a]P and DMBA were evaluated by alkaline comet assay using liver cells after both 3 and 24h. The mean percent of DNA (%DNA) in tail in the 0.05-0.2% MNNG and 0.1-0.25% 4NQO treatment groups was markedly higher than in the control group at 3h post-application. Although the mean %DNA values in the tail in the B[a]P and DMBA groups were the same as the controls at 3h post-application, the 2% B[a]P and 1% DMBA groups showed significantly higher values versus controls 24h after application. No significant increases in the mean %DNA in the tail were observed in the MMC group. No clear increases in %DNA in the tail were observed in the B[a]P and DMBA groups at 3 or 24h after application in the liver. These results suggest that the in vivo skin comet assay is able to accurately identify DNA-damaging potential with a skin-specific response and is a useful method to detect the DNA-damaging potential of genotoxic chemicals on the skin. 相似文献
157.
158.
Chen H Higashino H Kamenov ZA Azuma M Lee WH Yang XQ Zhou DJ Yuan WJ 《Life sciences》2003,72(25):2839-2851
Cardiovascular disease is one of the most important causes of morbidity and mortality in diabetes mellitus, but there has been controversy over functional impairment of diabetic hearts and their tolerance to ischemia. We studied ischemic heart function in type 2 diabetic rats with different degrees of hyperglycemia and its relationship with cardiac norepinephrine release. Otsuka Long-Evans Tokushima Fatty rats (OLETF) and age-matched Long-Evans Tokushima Otsuka normal rats (LETO) were used. One group of OLETF rats was given 30% sucrose in drinking water (OLETF-S). Hearts were isolated and perfused in a working heart preparation and subjected to 30 min ischemia followed by 40 min reperfusion at age of 12 months. Hemodynamics and coronary norepinephrine overflow were examined. Fasting plasma glucose in OLETF increased markedly at 12 months and sucrose administration exacerbated hyperglycemia in diabetic rats (LETO 6.6 +/- 0.5, OLETF 8.3 +/- 0.7, OLETF-S 15.0 +/- 1.7 mmol/L, P < 0.01). Basic cardiac output in OLETF was decreased as compared with LETO and OLETF-S (LETO 29.4 +/- 2.5, OLETF 24.0 +/- 2.4, OLETF-S 27.0 +/- 0.9 ml/min/g, P < 0.05) and remained very low after ischemia, while in OLETF-S it was well preserved (OLETF 4.2 +/- 2.1, OLETF-S 13.7 +/- 2.6 ml/min/g, P < 0.01). Correspondently, cardiac norepinephrine released during ischemia and reperfusion was lower in OLETF-S (OLETF 2.3 +/- 1.0, OLETF-S 0.7 +/- 0.1 pmol/ml, P < 0.01). Thus, OLETF hearts were more vulnerable to ischemia but sucrose feeding rendered their hearts resistant to ischemia. Less norepinephrine release may play a role in preventing postischemic functional deterioration in sucrose-fed diabetic hearts. 相似文献
159.
Michiru Nishita Sen Qiao Mari Miyamoto Yuka Okinaka Makiko Yamada Ryuju Hashimoto Kazumoto Iijima Hiroki Otani Christine Hartmann Ryuichi Nishinakamura Yasuhiro Minami 《Molecular and cellular biology》2014,34(16):3096-3105
Development of the metanephric kidney begins with the induction of a single ureteric bud (UB) on the caudal Wolffian duct (WD) in response to GDNF (glial cell line-derived neurotrophic factor) produced by the adjacent metanephric mesenchyme (MM). Mutual interaction between the UB and MM maintains expression of GDNF in the MM, thereby supporting further outgrowth and branching morphogenesis of the UB, while the MM also grows and aggregates around the branched tips of the UB. Ror2, a member of the Ror family of receptor tyrosine kinases, has been shown to act as a receptor for Wnt5a to mediate noncanonical Wnt signaling. We show that Ror2 is predominantly expressed in the MM during UB induction and that Ror2- and Wnt5a-deficient mice exhibit duplicated ureters and kidneys due to ectopic UB induction. During initial UB formation, these mutant embryos show dysregulated positioning of the MM, resulting in spatiotemporally aberrant interaction between the MM and WD, which provides the WD with inappropriate GDNF signaling. Furthermore, the numbers of proliferating cells in the mutant MM are markedly reduced compared to the wild-type MM. These results indicate an important role of Wnt5a-Ror2 signaling in morphogenesis of the MM to ensure proper epithelial tubular formation of the UB required for kidney development. 相似文献
160.
Yuki Kawakami Shiori Hirano Mai Kinoshita Akemi Otsuki Toshiko Suzuki-Yamamoto Makiko Suzuki Masumi Kimoto Sae Sasabe Mitsuo Fukushima Koji Kishimoto Takashi Izumi Toru Oga Shuh Narumiya Mitsuaki Sugahara Masashi Miyano Shozo Yamamoto Yoshitaka Takahashi 《Biochimica et Biophysica Acta (BBA)/General Subjects》2014