全文获取类型
收费全文 | 3376篇 |
免费 | 146篇 |
国内免费 | 5篇 |
出版年
2023年 | 7篇 |
2022年 | 23篇 |
2021年 | 25篇 |
2020年 | 13篇 |
2019年 | 30篇 |
2018年 | 45篇 |
2017年 | 25篇 |
2016年 | 71篇 |
2015年 | 112篇 |
2014年 | 112篇 |
2013年 | 264篇 |
2012年 | 181篇 |
2011年 | 192篇 |
2010年 | 116篇 |
2009年 | 150篇 |
2008年 | 221篇 |
2007年 | 186篇 |
2006年 | 199篇 |
2005年 | 201篇 |
2004年 | 208篇 |
2003年 | 197篇 |
2002年 | 207篇 |
2001年 | 36篇 |
2000年 | 39篇 |
1999年 | 36篇 |
1998年 | 51篇 |
1997年 | 48篇 |
1996年 | 45篇 |
1995年 | 33篇 |
1994年 | 39篇 |
1993年 | 40篇 |
1992年 | 25篇 |
1991年 | 15篇 |
1990年 | 29篇 |
1989年 | 21篇 |
1988年 | 23篇 |
1987年 | 24篇 |
1986年 | 26篇 |
1985年 | 20篇 |
1984年 | 15篇 |
1983年 | 13篇 |
1982年 | 24篇 |
1981年 | 24篇 |
1980年 | 20篇 |
1979年 | 9篇 |
1978年 | 16篇 |
1977年 | 7篇 |
1976年 | 10篇 |
1974年 | 9篇 |
1967年 | 6篇 |
排序方式: 共有3527条查询结果,搜索用时 15 毫秒
111.
Hirotsugu Ohkubo Yoshihiro Kanemitsu Takehiro Uemura Osamu Takakuwa Masaya Takemura Ken Maeno Yutaka Ito Tetsuya Oguri Nobutaka Kazawa Ryuji Mikami Akio Niimi 《PloS one》2016,11(3)
BackgroundAlthough several computer-aided computed tomography (CT) analysis methods have been reported to objectively assess the disease severity and progression of idiopathic pulmonary fibrosis (IPF), it is unclear which method is most practical. A universal severity classification system has not yet been adopted for IPF.ObjectiveThe purpose of this study was to test the correlation between quantitative-CT indices and lung physiology variables and to determine the ability of such indices to predict disease severity in IPF.MethodsA total of 27 IPF patients showing radiological UIP pattern on high-resolution (HR) CT were retrospectively enrolled. Staging of IPF was performed according to two classification systems: the Japanese and GAP (gender, age, and physiology) staging systems. CT images were assessed using a commercially available CT imaging analysis workstation, and the whole-lung mean CT value (MCT), the normally attenuated lung volume as defined from −950 HU to −701 Hounsfield unit (NL), the volume of the whole lung (WL), and the percentage of NL to WL (NL%), were calculated.ResultsCT indices (MCT, WL, and NL) closely correlated with lung physiology variables. Among them, NL strongly correlated with forced vital capacity (FVC) (r = 0.92, P <0.0001). NL% showed a large area under the receiver operating characteristic curve for detecting patients in the moderate or advanced stages of IPF. Multivariable logistic regression analyses showed that NL% is significantly more useful than the percentages of predicted FVC and predicted diffusing capacity of the lungs for carbon monoxide (Japanese stage II/III/IV [odds ratio, 0.73; 95% confidence intervals (CI), 0.48 to 0.92; P < 0.01]; III/IV [odds ratio. 0.80; 95% CI 0.59 to 0.96; P < 0.01]; GAP stage II/III [odds ratio, 0.79; 95% CI, 0.56 to 0.97; P < 0.05]).ConclusionThe measurement of NL% by threshold-based volumetric CT analysis may help improve IPF staging. 相似文献
112.
Issei Ueda Shingo Kakeda Keita Watanabe Reiji Yoshimura Taro Kishi Osamu Abe Satoru Ide Junji Moriya Asuka Katsuki Hikaru Hori Nakao Iwata Jun Nakamura Yukunori Korogi 《PloS one》2016,11(3)
Background
Earlier studies implicated norepinephrine transporter (NET) gene (SLC6A2) polymorphisms in the etiology of major depressive disorder (MDD). Recently, two single nucleotide SLC6A2 polymorphisms, G1287A in exon 9 and T-182C in the promoter region, were found to be associated with MDD in different populations. We investigated the relationship between the brain volume and these two polymorphisms of the SLC6A2 in MDD patients.Methods
We obtained 3D high-resolution T1-weighted images of 30 first-episode MDD patients and 48 age- and sex-matched healthy subjects (HS). All were divided into 4 groups based on polymorphism of either the G1287A or the T-182C genotype. VBM analysis examined the effects of diagnosis, genotype, and genotype-diagnosis interactions.Results
Diagnosis effects on the brain morphology were found in the left superior temporal cortex. No significant genotype effects were found in the T-182C and the G1287A. A significant genotype (G1287A)–diagnosis interaction was found in the left dorsolateral prefrontal cortex. No significant genotype (T-182C)–diagnosis interaction effects were observed in any brain region.Conclusions
In MDD patients there seems to be a relationship between the volume of the dorsolateral prefrontal cortex and polymorphism of the SLC6A2 G1287A gene. 相似文献113.
114.
Lilian?Rumi?Tsuruta Mariana?Lopes dos Santos Fernanda?Perez?Yeda Oswaldo?Keith?Okamoto Ana?Maria?MoroEmail author 《Applied microbiology and biotechnology》2016,100(23):10031-10041
Genetic characterization of protein-producing clones represents additional value to cell line development. In the present study, ten Per.C6 clones producing a Rebmab100 monoclonal antibody were selected using two cloning methods: six clones originated from limiting dilution cloning and four by the automated colony picker ClonePix FL. A stability program was performed for 50 generations, including 4 batches distributed along the timeframe to determine specific productivity (Qp) maintenance. Four stable clones (two from limiting dilution and two from ClonePix FL) were further evaluated. The relative mRNA expression levels of both heavy chain (HC) and light chain (LC) genes were verified at generations 0, 30–35, and 50–55 of the stability program. At generations 0 and 30–35, LC gene expression level was higher than HC gene, whereas at generation 50–55, the opposite prevailed. A high correlation was observed between Qp and HC or LC mRNA expression level for all clones at each generation analyzed along the continuous culture. The mRNA stability study was performed at steady-state culture. The LC gene displayed a higher half-life and lower decay constant than HC gene, accounting for the higher observed expression level of LC mRNA in comparison to HC mRNA. Clone R6 was highlighted due its high Qp, mRNA expression levels, and mRNA stability. Besides the benefits of applying genetic characterization for the selection of stable and high-producing clones, the present study shows for the first time the correlation between Qp and HC or LC expression levels and also mRNA stability in clones derived from human cell line Per.C6(®). 相似文献
115.
Qu Wei-Min Huang Zhi-Li Mochizuki Takatoshi Eguchi Naomi Chen Jiang-Fan Schwarzschild Michael A. Fink Stephen J. Urade Yoshihiro Hayaishi Osamu 《Sleep and biological rhythms》2016,2(1):S55-S55
Sleep and Biological Rhythms - 相似文献
116.
Yosuke Kanno Akira Ishisaki Eri Kawashita Hiromi Kuretake Kanako Ikeda Osamu Matsuo 《International journal of biological sciences》2016,12(1):63-71
Chronic inflammatory diseases, such as rheumatoid arthritis and periodontitis-caused bone destruction, results from an increase of bone-resorbing osteoclasts (OCs) induced by inflammation. However, the detailed mechanisms underlying this disorder remain unclear. We herein investigated that the effect of urokinase-type plasminogen activator (uPA) on inflammatory osteoclastogenesis induced by lipopolysaccharide (LPS), which is a potent stimulator of bone resorption in inflammatory diseases. We found that the uPA deficiency promoted inflammatory osteoclastogenesis and bone loss induced by LPS. We also showed that LPS induced the expression of uPA, and the uPA treatment attenuated the LPS-induced inflammatory osteoclastogenesis of RAW264.7 mouse monocyte/macrophage lineage cells. Additionally, we showed that the uPA-attenuated inflammatory osteoclastgenesis is associated with the activation of plasmin/protease-activated receptor (PAR)-1 axis by uPA. Moreover, we examined the mechanism underlying the effect of uPA on inflammatory osteoclastogenesis, and found that uPA/plasmin/PAR-1 activated the adenosine monophosphate-activated protein kinase (AMPK) pathway through Ca2+/calmodulin dependent protein kinase kinase (CaMKK) activation, and attenuated inflammatory osteoclastogenesis by inactivation of NF-κB in RAW264.7 cells. These data suggest that uPA attenuated inflammatory osteoclastogenesis through the plasmin/PAR-1/Ca2+/CaMKK/AMPK axis. Our findings may provide a novel therapeutic approach to bone loss caused by inflammatory diseases. 相似文献
117.
Flesh‐eating Streptococcus pyogenes triggers the expression of receptor activator of nuclear factor‐κB ligand
下载免费PDF全文
![点击此处可从《Cellular microbiology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Hidenori Matsui Yuriko Nakatani Haruno Yoshida Asako Takizawa Osamu Takeuchi Anders Øverby Takashi Takahashi Somay Y. Murayama Koichi Matsuo 《Cellular microbiology》2016,18(10):1390-1404
Human CD46 is a receptor for the M protein of group A streptococcus (GAS). The emm1 GAS strain GAS472 was isolated from a patient suffering from streptococcal toxic shock‐like syndrome. Human CD46‐expressing transgenic (Tg) mice developed necrotizing fasciitis associated with osteoclast‐mediated progressive and severe bone destruction in the hind paws 3 days after subcutaneous infection with 5 × 105 colony‐forming units of GAS472. GAS472 infection induced expression of the receptor activator of nuclear factor‐κB ligand (RANKL) while concomitantly reducing osteoprotegerin expression in the hind limb bones of CD46 Tg mice. Micro‐computed tomography analysis of the bones suggested that GAS472 infection induced local bone erosion and systemic bone loss in CD46 Tg mice. Because treatment with monoclonal antibodies (mAbs) against mouse CD4+ and CD8+ T lymphocytes did not inhibit osteoclastogenesis, T lymphocyte‐derived RANKL was not considered a major contributor to massive bone loss during GAS472 infection. However, immunohistochemical analysis of the hind limb bones showed that GAS472 infection stimulated RANKL production in various bone marrow cells, including fibroblast‐like cells. Treatment with a mAb against mouse RANKL significantly inhibited osteoclast formation and bone resorption. These data suggest that increased expression of RANKL in heterogeneous bone marrow cells provoked bone destruction during GAS infection. 相似文献
118.
Sachiko?OhdeEmail author Emily?McFadden Gautam?A.?Deshpande Hiroshi?Yokomichi Osamu?Takahashi Tsuguya?Fukui Rafael?Perera Zentaro?Yamagata 《BMC endocrine disorders》2016,16(1):65
Background
Guidelines for frequency of Type 2 diabetes mellitus (DM) screening remain unclear, with proposed screening intervals typically based on expert opinion. This study aims to demonstrate that HbA1c screening intervals may differ substantially when considering individual risk for diabetes.Methods
This was a multi-institutional retrospective open cohort study. Data were collected between April 1999 to March 2014 from one urban and one rural cohort in Japan. After categorization by age, we stratified individuals based on cardiovascular disease risk (Framingham 10-year cardiovascular risk score) and body mass index (BMI). We adapted a signal-to-noise method for distinguishing true HbA1c change from measurement error by constructing a linear random effect model to calculate signal and noise of HbA1c. Screening interval for HbA1c was defined as informative when the signal-to-noise ratio exceeded 1.Results
Among 96,456 healthy adults, 46,284 (48.0%) were male; age (range) and mean HbA1c (SD) were 48 (30–74) years old and 5.4 (0.4)%, respectively. As risk increased among those 30–44 years old, HbA1c screening intervals for detecting Type 2 DM consistently decreased: from 10.5 (BMI <18.5) to 2.4 (BMI?>?30) years, and from 8.0 (Framingham Risk Score <10%) to 2.0 (Framingham Risk Score ≥20%) years. This trend was consistent in other age and risk groups as well; among obese 30–44 year olds, we found substantially shorter intervals compared to other groups.Conclusion
HbA1c screening intervals for identification of DM vary substantially by risk factors. Risk stratification should be applied when deciding an optimal HbA1c screening interval in the general population to minimize overdiagnosis and overtreatment.119.
Yoichiro?OkuboEmail author Osamu?Motohashi Norisuke?Nakayama Ken?Nishimura Rika?Kasajima Yohei?Miyagi Manabu?Shiozawa Emi?Yoshioka Masaki?Suzuki Kota?Washimi Kae?Kawachi Madoka?Nito Yoichi?Kameda Tomoyuki?Yokose 《Diagnostic pathology》2016,11(1):128
Background
As the World Health Organization grading system for gastroenteropancreatic-neuroendocrine tumors (GEP-NETs) may not always correlate with tumor progression, it is imperative that other independent predictors of tumor progression be established. To identify such predictors, we conducted a retrospective histopathological study of hindgut NETs, obtained from endoscopic procedures, and used statistical analyses to evaluate predictive factors.Methods
We first obtained clinicopathological data of cases of hindgut NETs. Tissue sections from tumor samples were prepared and subjected to pathological examination. In particular, we calculated the microvessel density (MVD) and lymphatic microvessel density (LMVD) values, and performed appropriate statistical analyses.Results
A total of 42 cases of hindgut NETs were selected for the study, 41 from the rectum and 1 from the sigmoid colon. Based on the Ki-67 labeling index, 34 cases were classified as NET G1 tumors and 8 as NET G2 tumors. MVD values ranged from 1.4/mm2 to 73.9/mm2 and LMVD values from 0/mm2 to 22.9/mm2. MVD and LMVD were identified as risk factors for venous and lymphatic invasion of hindgut NETs. Moreover, MVD positively correlated with the maximum diameter of the tumor.Conclusions
Tumor progression of NETs may cause angiogenesis and lymphangiogenesis, via an unknown mechanism, as well as lymphovascular invasion. Angiogenesis likely plays an important role in occurrence and progression in the initial phase of hindgut NETs.120.
Junichiro Kishi Shinsuke Inuki Natsumi Hirata Emi Kashiwabara Daisuke Yoshidome Osamu Ichihara Yukari Fujimoto 《Bioorganic & medicinal chemistry letters》2019,29(8):970-973