全文获取类型
收费全文 | 2888篇 |
免费 | 193篇 |
国内免费 | 2篇 |
出版年
2022年 | 12篇 |
2021年 | 36篇 |
2020年 | 15篇 |
2019年 | 20篇 |
2018年 | 61篇 |
2017年 | 30篇 |
2016年 | 46篇 |
2015年 | 79篇 |
2014年 | 109篇 |
2013年 | 180篇 |
2012年 | 179篇 |
2011年 | 176篇 |
2010年 | 136篇 |
2009年 | 133篇 |
2008年 | 177篇 |
2007年 | 208篇 |
2006年 | 188篇 |
2005年 | 154篇 |
2004年 | 168篇 |
2003年 | 154篇 |
2002年 | 174篇 |
2001年 | 38篇 |
2000年 | 60篇 |
1999年 | 56篇 |
1998年 | 53篇 |
1997年 | 33篇 |
1996年 | 32篇 |
1995年 | 29篇 |
1994年 | 30篇 |
1993年 | 26篇 |
1992年 | 29篇 |
1991年 | 16篇 |
1990年 | 16篇 |
1989年 | 23篇 |
1988年 | 20篇 |
1987年 | 12篇 |
1986年 | 11篇 |
1985年 | 16篇 |
1984年 | 15篇 |
1983年 | 7篇 |
1982年 | 15篇 |
1981年 | 10篇 |
1980年 | 12篇 |
1979年 | 11篇 |
1978年 | 13篇 |
1977年 | 6篇 |
1975年 | 12篇 |
1971年 | 5篇 |
1969年 | 8篇 |
1968年 | 6篇 |
排序方式: 共有3083条查询结果,搜索用时 31 毫秒
991.
992.
Ito Y Kimura T Nam K Katoh A Masuzawa T Kishida A 《Biotechnology and bioengineering》2011,108(3):592-599
Different types of physiological‐mechanical stress, such as shear stress in vascular endothelial cells or hydrostatic pressure in chondrocytes are well known as regulators of cell function. In this study, the effects of vibration, a type of non‐physiological mechanical stimulation, on differentiation of rat pheochromocytoma (PC12) cells are reported. A nano‐vibration system was designed to produce nanometer‐scale vibration. The frequency and amplitude of the nano‐vibrations were monitored by a capacitance displacement sensor connected to an oscilloscope. When PC12 cells exposed to nerve growth factor were subjected to vibration at 10 kHz, differentiation and elongation of their neurites were promoted earlier in the culture. Vibration promoted differentiation of PC12 cells. This approach could therefore also be promising for determining of the effects of the physical environment on cell differentiation. Biotechnol. Bioeng. 2011; 108:592–599. © 2010 Wiley Periodicals, Inc. 相似文献
993.
Collagens are widely used in medical applications, including as a scaffold for tissue regeneration. However, animal-derived collagens have several drawbacks, such as low thermal stability, nonspecific cell adhesion, antigenicity, and contamination with pathogenic substances. To overcome these problems, we chemically synthesized the collagen-like polypeptide, poly(prolyl-hydroxyprolyl-glycyl) (poly(Pro-Hyp-Gly)), which forms a collagen-like triple-helical structure and shows biodegradability and biocompatibility. Here, we designed a novel scaffold where fibronectin-derived Gly Arg-Gly-Asp-Ser (GRGDS) and Pro-His-Ser-Arg-Asn (PHSRN) peptides were simultaneously conjugated with poly(Pro-Hyp-Gly). We assessed cell adhesion and migration activities using NIH3T3 cells in the scaffold and stratification ofimmortalized rabbit corneal epithelial cells. Cell adhesion was enhanced in scaffolds with GRGDS, increased with increasing amounts of conjugated GRGDS, and was significantly higher than bovine type I atelocollagen but lower than bovine fibronectin. Interestingly, simultaneous conjugation of GRGDS and PHSRN synergistically enhanced cell migration. Scaffolds containing almost equal amounts of GRGDS and PHSRN showed significantly higher cell migration than bovine type I atelocollagen. Addition of free GRGDS completely inhibited cell migration on the scaffold, whereas addition of free PHSRN partially inhibited cell migration. These results suggest that GRGDS plays a definitive role, and PHSRN plays an additional role, in cell migration. Conjugation of GRGDS resulted in the same level of stratification of rabbit corneal epithelial cells compared with bovine type I atelocollagen and bovine fibronectin. Because the simultaneous conjugation of GRGDS and PHSRN on poly(Pro-Hyp-Gly) enhances cell adhesion, migration, and stratification, it may be a useful scaffold for tissue regeneration. 相似文献
994.
995.
Masahito Hosokawa Hirotsugu Kenmotsu Yasuhiro Koh Tomoko Yoshino Takayuki Yoshikawa Tateaki Naito Toshiaki Takahashi Haruyasu Murakami Yukiko Nakamura Asuka Tsuya Takehito Shukuya Akira Ono Hiroaki Akamatsu Reiko Watanabe Sachiyo Ono Keita Mori Hisashige Kanbara Ken Yamaguchi Tsuyoshi Tanaka Tadashi Matsunaga Nobuyuki Yamamoto 《PloS one》2013,8(6)
Background
Epithelial cell adhesion molecule (EpCAM)-based enumeration of circulating tumor cells (CTC) has prognostic value in patients with solid tumors, such as advanced breast, colon, and prostate cancer. However, poor sensitivity has been reported for non-small cell lung cancer (NSCLC). To address this problem, we developed a microcavity array (MCA) system integrated with a miniaturized device for CTC isolation without relying on EpCAM expression. Here, we report the results of a clinical study on CTCs of advanced lung cancer patients in which we compared the MCA system with the CellSearch system, which employs the conventional EpCAM-based method.Methods
Paired peripheral blood samples were collected from 43 metastatic lung cancer patients to enumerate CTCs using the CellSearch system according to the manufacturer’s protocol and the MCA system by immunolabeling and cytomorphological analysis. The presence of CTCs was assessed blindly and independently by both systems.Results
CTCs were detected in 17 of 22 NSCLC patients using the MCA system versus 7 of 22 patients using the CellSearch system. On the other hand, CTCs were detected in 20 of 21 small cell lung cancer (SCLC) patients using the MCA system versus 12 of 21 patients using the CellSearch system. Significantly more CTCs in NSCLC patients were detected by the MCA system (median 13, range 0–291 cells/7.5 mL) than by the CellSearch system (median 0, range 0–37 cells/7.5 ml) demonstrating statistical superiority (p = 0.0015). Statistical significance was not reached in SCLC though the trend favoring the MCA system over the CellSearch system was observed (p = 0.2888). The MCA system also isolated CTC clusters from patients who had been identified as CTC negative using the CellSearch system.Conclusions
The MCA system has a potential to isolate significantly more CTCs and CTC clusters in advanced lung cancer patients compared to the CellSearch system. 相似文献996.
Toru Yamazaki Masashi Yamori Shiro Tanaka Keiichi Yamamoto Eriko Sumi Megumi Nishimoto-Sano Keita Asai Katsu Takahashi Takeo Nakayama Kazuhisa Bessho 《PloS one》2013,8(11)
Background
Several studies have reported osteomyelitis of the jaw (OMJ) as a side effect of bisphosphonates (BPs), and the risk of oral BPs has been recently clarified. However, other systemic risk factors of OMJ remain unclear. Importantly, the possibility of risk classification based on the clinical characteristics of patients has not been explored. Here, we clarified risk factors of OMJ and evaluate the predictive accuracy of risk indices in osteoporosis patients.Methods
We performed sub-analysis using a database developed for a retrospective cohort study in patients taking medications for osteoporosis at Kyoto University Hospital. Risk indices for OMJ were constructed using logistic regression analysis, and odds ratios (OR) for OMJ cases and 95% confidence intervals (CI) were estimated. Potential risk factors included in the statistical analysis were age; sex; diabetes; use of oral BPs, corticosteroids, cancer chemotherapy, antirheumatic drugs, and biologic agents; and their interactions. Risk indices were calculated by the sum of potential risk factors of an individual patient multiplied by the regression coefficients. The discriminatory power of the risk indices was assessed by receiver operating characteristic (ROC) analysis.Results
In analysis of all patients, oral BPs (OR: 4.98, 95% CIs: 1.94-12.75), age (OR: 1.28, 95% CI: 1.06-1.60) and sex-chemotherapy interaction (OR: 11.70, 95% CI: 1.46-93.64) were significant risk factors of OMJ. Areas under the ROC curves of these risk indices provided moderate sensitivity or specificity regardless of group (0.683 to 0.718).Conclusions
Our data suggest that oral BP use, age, and sex-chemotherapy are predictors of OMJ in osteoporosis patients. The risk indices are moderately high, and allow the prediction of OMJ incidence. 相似文献997.
Noriyuki Otsuki Yuichiro Nakatsu Toru Kubota Tsuyoshi Sekizuka Fumio Seki Kouji Sakai Makoto Kuroda Ryoji Yamaguchi Makoto Takeda 《PloS one》2013,8(12)
Canine distemper virus (CDV) becomes able to use human receptors through a single amino acid substitution in the H protein. In addition, CDV strains possessing an intact C protein replicate well in human epithelial H358 cells. The present study showed that CDV strain 007Lm, which was isolated from lymph node tissue of a dog with distemper, failed to replicate in H358 cells, although it possessed an intact C protein. Sequence analyses suggested that a cysteine-to-tyrosine substitution at position 267 of the V protein caused this growth defect. Analyses using H358 cells constitutively expressing the CDV V protein showed that the V protein with a cysteine, but not that with a tyrosine, at this position effectively blocked the interferon-stimulated signal transduction pathway, and supported virus replication of 007Lm in H358 cells. Thus, the V protein as well as the C protein appears to be functional and essential for CDV replication in human epithelial cells. 相似文献
998.
Toshihiro Murata Erdenechimeg Selenge Kento Suganuma Yusuke Asai Javzan Batkhuu Fumihiko Yoshizaki 《Phytochemistry letters》2013,6(4):552-555
Two new chromone acyl glucosides, 5-hydroxy-7-O-(6-O-p-cis-coumaroyl-β-D-glucopyranosyl)-chromone (1) and 5-hydroxy-7-O-(6-O-p-trans-coumaroyl-β-D-glucopyranosyl)-chromone (2), and a new flavonoid glucoside, ayanin 3′-O-β-D-glucopyranoside (3) were isolated from aerial parts of Dasiphora parvifolia, together with flavonoid glycosides (4–10), catechins (11, 12), and hydrolysable tannins (13, 14). The chemical structures of these compounds were elucidated on the basis of spectroscopic data. The 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity and the hyaluronidase inhibitory activity of these compounds were evaluated. 相似文献
999.
Tomoko Tajiri Hisako Matsumoto Akio Niimi Isao Ito Tsuyoshi Oguma Hitoshi Nakaji Hideki Inoue Toshiyuki Iwata Tadao Nagasaki Yoshihiro Kanemitsu Guergana Petrova Michiaki Mishima 《PloS one》2013,8(6)
Background
Airway eosinophilia is a predictor of steroid responsiveness in steroid-naïve asthma. However, the relationship between airway eosinophilia and the expression of FK506-binding protein 51 (FKBP51), a glucocorticoid receptor co-chaperone that plays a role in steroid insensitivity in asthma, remains unknown.Objective
To evaluate the relationship between eosinophilic inflammation and FKBP51 expression in sputum cells in asthma.Methods
The FKBP51 mRNA levels in sputum cells from steroid-naïve patients with asthma (n = 31) and stable asthmatic patients on inhaled corticosteroid (ICS) (n = 28) were cross-sectionally examined using real-time PCR. Associations between FKBP51 levels and clinical indices were analyzed.Results
In steroid-naïve patients, the FKBP51 levels were negatively correlated with eosinophil proportions in blood (r = −0.52) and sputum (r = −0.57), and exhaled nitric oxide levels (r = −0.42) (all p<0.05). No such associations were observed in patients on ICS. In steroid-naïve patients, improvement in forced expiratory volume in one second after ICS initiation was correlated with baseline eosinophil proportions in blood (r = 0.74) and sputum (r = 0.76) and negatively correlated with FKBP51 levels (r = −0.73) (all p<0.0001) (n = 20). Lastly, the FKBP51 levels were the lowest in steroid-naïve asthmatic patients, followed by mild to moderate persistent asthmatic patients on ICS, and the highest in severe persistent asthmatic patients on ICS (p<0.0001).Conclusions
Lower FKBP51 expression in sputum cells may reflect eosinophilic inflammation and glucocorticoid responsiveness in steroid-naïve asthmatic patients. 相似文献1000.
Vo Nguyen Trung Hiroshi Yamamoto Akira Furukawa Tsuyoshi Yamaguchi Satoshi Murata Masahiro Yoshimura Yoko Murakami Shigetaka Sato Hideji Otani Satoshi Ugi Katsutaro Morino Hiroshi Maegawa Tohru Tani 《PloS one》2013,8(6)