全文获取类型
收费全文 | 3155篇 |
免费 | 191篇 |
国内免费 | 1篇 |
专业分类
3347篇 |
出版年
2022年 | 13篇 |
2021年 | 28篇 |
2020年 | 30篇 |
2019年 | 28篇 |
2018年 | 24篇 |
2017年 | 35篇 |
2016年 | 51篇 |
2015年 | 86篇 |
2014年 | 108篇 |
2013年 | 194篇 |
2012年 | 183篇 |
2011年 | 198篇 |
2010年 | 100篇 |
2009年 | 124篇 |
2008年 | 177篇 |
2007年 | 187篇 |
2006年 | 168篇 |
2005年 | 158篇 |
2004年 | 164篇 |
2003年 | 180篇 |
2002年 | 166篇 |
2001年 | 50篇 |
2000年 | 82篇 |
1999年 | 62篇 |
1998年 | 42篇 |
1997年 | 31篇 |
1996年 | 32篇 |
1995年 | 31篇 |
1994年 | 22篇 |
1993年 | 29篇 |
1992年 | 42篇 |
1991年 | 40篇 |
1990年 | 36篇 |
1989年 | 37篇 |
1988年 | 33篇 |
1987年 | 39篇 |
1986年 | 26篇 |
1985年 | 27篇 |
1984年 | 28篇 |
1983年 | 21篇 |
1982年 | 15篇 |
1981年 | 13篇 |
1980年 | 13篇 |
1979年 | 19篇 |
1978年 | 19篇 |
1977年 | 15篇 |
1974年 | 12篇 |
1973年 | 12篇 |
1971年 | 14篇 |
1968年 | 15篇 |
排序方式: 共有3347条查询结果,搜索用时 9 毫秒
201.
Ohno T Kita M Yamaoka Y Imamura S Yamamoto T Mitsufuji S Kodama T Kashima K Imanishi J 《Helicobacter》2003,8(3):207-215
Background. Helicobacter pylori is an important pathogen responsible for gastroduodenal diseases in humans. Although the eradication of H. pylori using antibiotics often improves gastroduodenal diseases, resistance to the antibiotics is emerging. Materials and Methods. The antimicrobial effect of essential oils and the development of resistance to the essential oils were evaluated in vitro and in vivo. Results. Thirteen essential oils used in this study completely inhibited the growth of H. pylori in vitro at a concentration of 0.1% (v/v). Cymbopogon citratus (lemongrass) and Lippia citriodora (lemon verbena) were bactericidal against H. pylori at 0.01% at pH 4.0 and 5.0. Resistance to lemongrass did not develop even after 10 sequential passages, whereas resistance to clarithromycin developed under the same conditions. In in vivo studies, the density of H. pylori in the stomach of mice treated with lemongrass was significantly reduced compared with untreated mice. Conclusions. These results demonstrate that the essential oils are bactericidal against H. pylori without the development of acquired resistance, suggesting that essential oils may have potential as new and safe agents for inclusion in anti‐H. pylori regimens. 相似文献
202.
Oxidation of the C5'-position of DNA results in direct strand scission. The 3'-fragments produced contain DNA lesions at their 5'-termini. The major DNA lesion contains an aldehyde at its C5'-position, but its nucleobase is unmodified. Excision of the lesion formed from oxidation of thymidine (T-al) is achieved by strand displacement synthesis by DNA polymerase β (Pol β) in the presence or absence of flap endonuclease 1 (FEN1). Pol β displaces T-al and thymidine with comparable efficiency, but less so than a chemically stabilized abasic site analogue (F). FEN1 cleaves the flaps produced during strand displacement synthesis that are two nucleotides or longer. A ternary complex containing T-al is also a substrate for the bacterial UvrABC nucleotide excision repair system. The sites of strand scission are identical in ternary complexes containing T-al, thymidine, or F. UvrABC incision efficiency of these ternary complexes is comparable as well but significantly slower than a duplex substrate containing a bulky substituted thymidine. However, cleavage occurs only on the 5'-fragment and does not remove the lesion. These data suggest that unlike many lesions the redundant nature of base excision and nucleotide excision repair systems does not provide a means for removing the major damage product produced by agents that oxidize the C5'-position. This may contribute to the high cytotoxicity of drugs that oxidize the C5'-position in DNA. 相似文献
203.
In this work, we examined structural changes of actin filaments interacting with myosin visualized by quick freeze deep-etch replica electron microscopy (EM) by using a new method of image processing/analysis based on mathematical morphology.In order to quantify the degree of structural changes, two characteristic patterns were extracted from the EM images. One is the winding pattern of the filament shape (WP) reflecting flexibility of the filament, and the other is the surface pattern of the filament (SP) reflecting intra-molecular domain-mobility of actin monomers constituting the filament. EM images were processed by morphological filtering followed by box-counting to calculate the fractal dimensions for WP (DWP) and SP (DSP). The result indicates that DWP was larger than DSP irrespective of the state of the filament (myosin-free or bound) and that both parameters for myosin-bound filaments were significantly larger than those for myosin-free filaments. Overall, this work provides the first quantitative insight into how conformational disorder of actin monomers is correlated with the myosin-induced increase in flexibility of actin filaments along their length as suggested by earlier studies with different techniques. Our method is yet to be improved in details, but promising as a powerful tool for studying the structural change of protein molecules and their assemblies, which can potentially be applied to a wide range of biological and biomedical images. 相似文献
204.
Mirei Shou Hiroyuki Terashima Sen‐Ichi Aizawa Atsushi Taga Atsushi Yamamoto Shuji Kodama 《Chirality》2015,27(7):417-421
Three aldohexoses, glucose, galactose, and mannose, and three aldopentoses, arabinose, xylose, and ribose, were derivatized with L‐tryptophanamide (L‐TrpNH2) under alkaline conditions. Using a basic mobile phase (pH 9.2), the three aldohexoses or the three aldopentoses were simultaneously enantioseparated, respectively, but all the six monosaccharides could not be simultaneously enantioseparated. A large amount of nonreacted L‐TrpNH2 was detected after the derivatized monosaccharides. In order to widen the separation window, a large portion of nonreacted L‐TrpNH2 could be eliminated by liquid–liquid extraction with ethylacetate, and elution order of the derivatized monosaccharides and nonreacted L‐TrpNH2 was found to be reversed using a neutral mobile phase. All of the six monosaccharides were simultaneously enantioseparated by reversed phase high‐performance liquid chromatography (HPLC) using InertSustainSwift C18 column (4.6 mm i.d. × 150 mm) and a mobile phase containing 180 mM phosphate buffer (pH 7.6), 1.5 mM butylboronic acid, and 5% acetonitrile at 40 °C. Nomenclature of D and L for monosaccharides is based on the configurations of the asymmetric C4 center for aldopentoses and C5 center for aldohexoses. It was found that the enantiomer elution order of these six monosaccharides and fucose in the proposed method conformed to be the absolute configuration of the C2 center. Chirality 27:417–421, 2015. © 2015 Wiley Periodicals, Inc. 相似文献
205.
206.
207.
Mutated SEA-D227A-conjugated antibodies greatly enhance antitumor activity against MUC1-expressing bile duct carcinoma 总被引:8,自引:0,他引:8
Hideaki Kodama Masanori Suzuki Yu Katayose Masao Shinoda Naoki Sakurai Shin-ichi Takemura Hiroshi Yoshida Hisaaki Saeki Masahiko Ichiyama Kohei Tsumoto Ryutaro Asano Izumi Kumagai Kohzoh Imai Yuji Hinoda Seiki Matsuno Toshio Kudo 《Cancer immunology, immunotherapy : CII》2001,50(10):539-548
For the purpose of establishing a new adoptive immunotherapy for bile duct carcinoma (BDC), we have directed our attention to superantigens (SAgs), the most potent known activators of T lymphocytes. In our previous study, staphylococcal enterotoxin A (SEA) was conjugated chemically with MUSE11 mAb, which recognizes the MUC1 cancer-associated antigen, and shown to enhance the specific cytotoxic activity of T-LAK cells against MUC1-expressing BDC cells (TFK-1) in vitro and in vivo. However, it is probable that SEA might cause side-effects because of nonspecific binding to class II positive cells. In order to overcome these, we generated mutated SEA (mSEA) by changing Asp at position 227 of native SEA to Ala, which has reduced affinity to MHC class II molecules, but retains the potential for T cell activation. When mSEA-D227A was administered to rabbits to examine effects on blood pressure, 500 times more mSEA-D227A was tolerated than native SEA. This prompted us to construct a mSEA-D227A-conjugated mAb, reactive with MUC1. It augmented the antitumor activity of T-LAK cells significantly, and furthermore, mSEA-D227A could be conjugated to two bispecific antibodies, BsAb (anti-MUC1 x anti-CD3) and BsAb (anti-MUC1 x anti-CD28), which in combination had greater enhancing effects than mSEA-D227A-conjugated anti-MUC1 mAb, and combination of unconjugated BsAbs. These findings indicate a utility of mSEA-D227A-conjugated antibodies for targeted cancer immunotherapy. 相似文献
208.
Jeffrey S. Rubin Donald P. Bottaro Marcio Chedid Toru Miki Dina Ron Hyae-Gyeong Cheon William G. Taylor Emma Fortney Hiromi Sakata Paul W. Finch William J. LaRochelle 《Cell biology international》1995,19(5):399-411
Keratinocyte growth factor (KGF) is a member of the heparin-binding fibroblast growth factor family (FGF-7) with a distinctive pattern of target-cell specificity. Studies performed in cell culture suggested that KGF was mitogenically active only on epithelial cells, albeit from a variety of tissues. In contrast, KGF was produced solely by cells of mesenchymal origin, leading to the hypothesis that it might function as a paracrine mediator of mesenchymal-epithelial communication. Biochemical analysis and molecular cloning established that the KGF receptor (KGFR) was a tyrosine kinase isoform encoded by the fgfr-2 gene. Many detailed investigations of KGF and KGFR expression in whole tissue and cell lines largely substantiated the pattern initially perceived in vitro of mesenchymal and epithelial distribution, respectively. Moreover, functional assays in organ culture and in vivo and studies of KGF regulation by sex sterorid hormones reinforced the idea that KGF acts predominantly on epithelial cells to elicit a variety of responses including proliferation, migration and morphogenesis. 相似文献
209.
Andrew D. James Waseema Patel Zohra Butt Magretta Adiamah Raga Dakhel Ayse Latif Carolina Uggenti Eileithyia Swanton Hiromi Imamura Ajith K. Siriwardena Jason I. E. Bruce 《The Journal of biological chemistry》2015,290(41):24760-24771
Evidence suggests that the plasma membrane Ca2+-ATPase (PMCA), which is critical for maintaining a low intracellular Ca2+ concentration ([Ca2+]i), utilizes glycolytically derived ATP in pancreatic ductal adenocarcinoma (PDAC) and that inhibition of glycolysis in PDAC cell lines results in ATP depletion, PMCA inhibition, and an irreversible [Ca2+]i overload. We explored whether this is a specific weakness of highly glycolytic PDAC by shifting PDAC cell (MIA PaCa-2 and PANC-1) metabolism from a highly glycolytic phenotype toward mitochondrial metabolism and assessing the effects of mitochondrial versus glycolytic inhibitors on ATP depletion, PMCA inhibition, and [Ca2+]i overload. The highly glycolytic phenotype of these cells was first reversed by depriving MIA PaCa-2 and PANC-1 cells of glucose and supplementing with α-ketoisocaproate or galactose. These culture conditions resulted in a significant decrease in both glycolytic flux and proliferation rate, and conferred resistance to ATP depletion by glycolytic inhibition while sensitizing cells to mitochondrial inhibition. Moreover, in direct contrast to cells exhibiting a high glycolytic rate, glycolytic inhibition had no effect on PMCA activity and resting [Ca2+]i in α-ketoisocaproate- and galactose-cultured cells, suggesting that the glycolytic dependence of the PMCA is a specific vulnerability of PDAC cells exhibiting the Warburg phenotype. 相似文献
210.