全文获取类型
收费全文 | 4002篇 |
免费 | 225篇 |
国内免费 | 7篇 |
出版年
2022年 | 14篇 |
2021年 | 44篇 |
2020年 | 28篇 |
2019年 | 37篇 |
2018年 | 65篇 |
2017年 | 42篇 |
2016年 | 70篇 |
2015年 | 126篇 |
2014年 | 128篇 |
2013年 | 231篇 |
2012年 | 213篇 |
2011年 | 272篇 |
2010年 | 154篇 |
2009年 | 177篇 |
2008年 | 249篇 |
2007年 | 269篇 |
2006年 | 244篇 |
2005年 | 254篇 |
2004年 | 255篇 |
2003年 | 248篇 |
2002年 | 245篇 |
2001年 | 54篇 |
2000年 | 60篇 |
1999年 | 54篇 |
1998年 | 55篇 |
1997年 | 32篇 |
1996年 | 40篇 |
1995年 | 53篇 |
1994年 | 38篇 |
1993年 | 52篇 |
1992年 | 43篇 |
1991年 | 32篇 |
1990年 | 40篇 |
1989年 | 34篇 |
1988年 | 28篇 |
1987年 | 25篇 |
1986年 | 31篇 |
1985年 | 17篇 |
1984年 | 19篇 |
1983年 | 20篇 |
1982年 | 16篇 |
1981年 | 15篇 |
1980年 | 14篇 |
1979年 | 8篇 |
1978年 | 13篇 |
1977年 | 8篇 |
1975年 | 7篇 |
1974年 | 10篇 |
1973年 | 6篇 |
1968年 | 7篇 |
排序方式: 共有4234条查询结果,搜索用时 31 毫秒
1.
Vipin Shankar Hiroki Hori Kentaro Kihira Qi Lei Hidemi Toyoda Shotaro Iwamoto Yoshihiro Komada 《PloS one》2015,10(3)
Neuroblastoma accounts for 15% of childhood cancer deaths and presents with metastatic disease of the bone and the bone marrow at diagnosis in 70% of the cases. Previous studies have shown that the Mesenchymal Stromal Cell (MSC) secretome, triggers metastases in several cancer types such as breast and prostate cancer, but the specific role of the MSC factors in neuroblastoma metastasis is unclear. To better understand the effect of MSC secretome on chemokine receptors in neuroblastoma, and its role in metastasis, we studied a panel of 20 neuroblastoma cell lines, and compared their invasive potential towards MSC-conditioned-RPMI (mRPMI) and their cytokine receptor expression profiles. Western blot analysis revealed the expression of multiple CXCR4 isoforms in neuroblastoma cells. Among the five major isoforms, the expression of the 47 kDa isoform showed significant correlation with high invasiveness. Pretreatment with mRPMI up-regulated the expression of the 47 kDa CXCR4 isoform and also increased MMP-9 secretion, expression of integrin α3 and integrin β1, and the invasive potential of the cell; while blocking CXCR4 either with AMD 3100, a CXCR4 antagonist, or with an anti-47 kDa CXCR4 neutralizing antibody decreased the secretion of MMP-9, the expression of integrin α3 and integrin β1, and the invasive potential of the cell. Pretreatment with mRPMI also protected the 47 kDa CXCR4 isoform from ubiquitination and subsequent degradation. Our data suggest a modulatory role of the MSC secretome on the expression of the 47 kDa CXCR4 isoform and invasion potential of the neuroblastoma cells to the bone marrow. 相似文献
2.
3.
Hajime Sakaguchi Hiromi Hagiwara Yoshihiro Fukumori Yutaka Tamaura Minoru Funaki Shigehisa Hirose 《FEMS microbiology letters》1993,107(2-3):169-173
Abstract The magnetic bacterium Magnetospirillum magnetotacticum prefers a microaerobic habitat and should be able to sense oxygen. Therefore, the bacterium was cultured under atmospheres containing 0–5% O2 and analyzed for oxygen-dependent changes in the levels of its protein components by sodium dodecyl sulfate-polyccrylamide gel electrophoresis (SDS-PAGE). The analysis revealed a marked anaerobic induction of a 140-kDa protein, which was suppressed when M. magnetotacticum was switched from microaerobic (<1% O2 ) to aerobic (>1% O2 ) growth conditions. Although its function remains to be determined, the 140-kDa protein may serve as a useful tool to gain insight into the physiology of the organism. 相似文献
4.
Yoshinari Maeda Kiyoshi Yoshimura Hiroto Matsui Yoshitaro Shindo Takao Tamesa Yukio Tokumitsu Noriaki Hashimoto Yoshihiro Tokuhisa Kazuhiko Sakamoto Kouhei Sakai Yutaka Suehiro Yuji Hinoda Koji Tamada Shigefumi Yoshino Shoichi Hazama Masaaki Oka 《Cancer immunology, immunotherapy : CII》2015,64(8):1047-1056
5.
Hiroki Yanagida Takefumi Morita Juhyon Kim Keitaro Yoshida Kazuki Nakajima Yutaka Oomura Matthew J. Wayner Kazuo Sasaki 《Peptides》2008,29(6):912-918
Ghrelin is an endogenous ligand for the growth hormone (GH) secretagogue (GHS) receptor (GHS-R) and a potent stimulant for GH secretion even in infantile rats before puberty. Although the ventromedial nucleus of the hypothalamus (VMH) might be a site of action for ghrelin to induce GH release, the electrophysiological effect of ghrelin on VMH neurons in infantile rats remains to be elucidated. Thus, the purpose of the present study was to investigate the effect of ghrelin on VMH neurons using hypothalamic slices of infantile rats. Ghrelin excited a majority of VMH neurons in a concentration-dependent manner. VMH neurons that were excited by GH releasing peptide-6 (GHRP-6), a synthetic GHS, were also excited by ghrelin and vice versa. Repeated application of ghrelin to the same VMH neuron decreased progressively the excitatory responses depending on the number of times it was administered. The excitatory effect of ghrelin on VMH neurons in normal artificial cerebrospinal fluid (ACSF) persisted in low Ca2+-high Mg2+ ACSF. The present results indicate that (1) ghrelin excites a majority of VMH neurons dose-dependently and postsynaptically and (2) the excitatory effects of ghrelin are mimicked by GHRP-6 and desensitized by repeated applications of ghrelin. 相似文献
6.
After E. coli cells (WP2 and WP2uvrA) were treated with chemical mutagens (methyl methanesulfonate, MMS; N-methyl-N-nitrosourea, MNU; 4-nitroquinoline 1-oxide, 4NQO) in 1/15 M phosphate buffer, the mutability of the treated cells plated on a D2O-agar plate was compared with that plated on an ordinary H2O-agar plate. The mutation frequency decreased more or less on the D2O-agar plate. The D2O-substitution effects, as termed by the relative mutation frequencies (MFD2O/MFH2O), are 0.92 for MMS, 0.29 for MNU, and 0.42 for 4NQO in WP2, and 0.68 for MMS, 0.49 for MNU, and 0.16 for 4NQO in WP2uvrA. The D2O effect seemed to be partly related to the function of the uvrA gene-associated products. The pH dependence of mutability was discussed in connection with the D2O-substitution effect. 相似文献
7.
Betamethasone 17, 21-dipropionate (BMDP), a potent glucocorticoid, produces adrenal hypertrophy in the rat fetus. The present study was performed to investigate the possible alterations of corticosteroidogenesis due to endogeneous substrates or exogenous pregnenolone in the incubation of homogenates of fetal hypertrophic adrenals caused by BMDP given to pregnant rats at day 19 of pregnancy.The corticosteroidal products and those levels per mg homogenate in an incubate of the hypertrophic adrenal homogenate did not differ from those of a normal adrenal. No accumulations of abnormal precursors or intermediates were found in the incubates of the hypertrophic adrenals. It is concluded from these findings that no qualitative alterations in the pathway of corticosteroidogenesis occurred in the hypertrophic adrenal glands caused by BMDP in the rat fetus. When the calculation was done per adrenal gland, the content of corticosterone in the incubate of the homogenate of the hypertrophic adrenal was remarkably higher than that found in a normal gland. This finding was compatible with the significant increase of the plasma corticosterone concentration in the fetuses with the adrenal hypertrophy caused by BMDP. 相似文献
8.
Takumi Hiyoshi Hisanori Domon Tomoki Maekawa Kosuke Nagai Hikaru Tamura Naoki Takahashi Daisuke Yonezawa Tomohiro Miyoshi Akihiro Yoshida Koichi Tabeta Yutaka Terao 《Microbiology and immunology》2019,63(3-4):100-110
Aggregatibacter actinomycetemcomitans is considered to be associated with periodontitis. Leukotoxin (LtxA), which destroys leukocytes in humans, is one of this bacterium's major virulence factors. Amounts of neutrophil elastase (NE), which is normally localized in the cytoplasm of neutrophils, are reportedly increased in the saliva of patients with periodontitis. However, the mechanism by which NE is released from human neutrophils and the role of NE in periodontitis is unclear. In the present study, it was hypothesized that LtxA induces NE release from human neutrophils, which subsequently causes the breakdown of periodontal tissues. LtxA‐treatment did not induce significant cytotoxicity against human gingival epithelial cells (HGECs) or human gingival fibroblasts (HGFs). However, it did induce significant cytotoxicity against human neutrophils, leading to NE release. Furthermore, NE and the supernatant from LtxA‐treated human neutrophils induced detachment and death of HGECs and HGFs, these effects being inhibited by administration of an NE inhibitor, sivelestat. The present results suggest that LtxA mediates human neutrophil lysis and induces the subsequent release of NE, which eventually results in detachment and death of HGECs and HGFs. Thus, LtxA‐induced release of NE could cause breakdown of periodontal tissue and thereby exacerbate periodontitis. 相似文献
9.
10.
Kiyomi Kikugawa Kazuyuki Hiramoto Yutaka Okamoto Yo-Ko Hasegawa 《Free radical research》1994,21(6):399-408
Nitrogen dioxide less than 100 ppm in air induced lipid peroxidation of liposome composed of l-palmitoyl-2-arachidonylphosphatidylcholine as assessed by thiobarbituric acid reactivity. The nitrogen dioxide-induced lipid peroxidation was enhanced by cysteine, glutathione and bovine serum albumin. While the activity of nitrogen dioxide in air to induce single strand breaks of supercoiled plasmid DNA was low, the breaking was remarkably enhanced by cysteine, glutathione and bovine serum albumin. ESR spin trapping using 5,5-dimethyl-1-pyrroline N-oxide showed that certain strong oxidant(s) were generated by interaction of nitrogen dioxide and cysteine. The spin trapping using 3,5-dibromo-4-nitrosobenzene-sulfonate suggested that sulfur-containing radicals were generated by interaction of nitrogen dioxide and cysteine or glutathione. Hence, certain sulfur-containing radicals generated by the interaction which could effectively induce lipid peroxidation and DNA strand breaks. 相似文献