全文获取类型
收费全文 | 1008篇 |
免费 | 86篇 |
出版年
2022年 | 3篇 |
2021年 | 10篇 |
2020年 | 2篇 |
2019年 | 5篇 |
2018年 | 15篇 |
2017年 | 12篇 |
2016年 | 21篇 |
2015年 | 32篇 |
2014年 | 41篇 |
2013年 | 99篇 |
2012年 | 50篇 |
2011年 | 61篇 |
2010年 | 26篇 |
2009年 | 28篇 |
2008年 | 51篇 |
2007年 | 50篇 |
2006年 | 40篇 |
2005年 | 48篇 |
2004年 | 38篇 |
2003年 | 37篇 |
2002年 | 42篇 |
2001年 | 37篇 |
2000年 | 35篇 |
1999年 | 36篇 |
1998年 | 8篇 |
1997年 | 8篇 |
1996年 | 12篇 |
1995年 | 12篇 |
1994年 | 6篇 |
1993年 | 6篇 |
1992年 | 29篇 |
1991年 | 24篇 |
1990年 | 13篇 |
1989年 | 24篇 |
1988年 | 15篇 |
1987年 | 17篇 |
1986年 | 21篇 |
1985年 | 7篇 |
1984年 | 9篇 |
1983年 | 8篇 |
1982年 | 9篇 |
1981年 | 8篇 |
1980年 | 2篇 |
1979年 | 7篇 |
1978年 | 4篇 |
1977年 | 3篇 |
1975年 | 2篇 |
1974年 | 4篇 |
1972年 | 3篇 |
1968年 | 3篇 |
排序方式: 共有1094条查询结果,搜索用时 46 毫秒
121.
Shuichi Miyagawa Yusaku Koyama Mika Kokubo Yuichi Matsushita Yoshinao Adachi Sengdeaune Sivilay Nobumitsu Kawakubo Shinya Oba 《Journal of ethnobiology and ethnomedicine》2011,7(1):1-6
Background
This study was conducted to identify medicinal plants and spices used for medicine by the community of Beni-Sueif, Upper Egypt.Methods
Ethnobotanical data from local people was collected using direct interviews and a semi-structured questionnaire.Results
Forty-eight plant species belonging to twenty-seven families and forty-seven genera were encountered during the study. Their botanical and vernacular names, plant parts used and medicinal uses are given. Results of the study were analyzed using two quantitative tools. The factor informant consensus indicated the agreement in the use of plants and the fidelity level indicated the ratio between the number of informants who independently suggested the use of a species for the same major purpose and the total number of informants who mentioned the plant for any use. The results of the factor informant consensus showed that the cardiovascular category has the greatest agreement, followed by the immunological, gastrointestinal and respiratory categories. The most important species according to their fidelity are: Hibiscus sabdariffa L. for the cardiovascular category; Trigonella foenum-graecum L. for the immunological category; Mentha piperita L. for the gastrointestinal category and Pimpinella anisum L. for the respiratory category.Conclusions
Medicinal plants are still used for treatment in Beni-Sueif community despite the availability of prescribed medications. Documentation of this ethnomedicinal knowledge is important. Evaluation of pharmacological activity for the promising medicinal plants is suggested. 相似文献122.
Background
Aberrant CD40 ligand (CD154) expression occurs on both T cells and B cells in human lupus patients, which is suggested to enhance B cell CD40 signaling and play a role in disease pathogenesis. Transgenic mice expressing CD154 by their B cells (CD154TG) have an expanded spleen B cell pool and produce autoantibodies (autoAbs). CD22 deficient (CD22−/−) mice also produce autoAbs, and importantly, their B cells are hyper-proliferative following CD40 stimulation ex vivo. Combining these 2 genetic alterations in CD154TGCD22−/− mice was thereby predicted to intensify CD40 signaling and autoimmune disease due to autoreactive B cell expansion and/or activation.Methodology/Principal Findings
CD154TGCD22−/− mice were assessed for their humoral immune responses and for changes in their endogenous lymphocyte subsets. Remarkably, CD154TGCD22−/− mice were not autoimmune, but instead generated minimal IgG responses against both self and foreign antigens. This paucity in IgG isotype switching occurred despite an expanded spleen B cell pool, higher serum IgM levels, and augmented ex vivo B cell proliferation. Impaired IgG responses in CD154TGCD22−/− mice were explained by a 16-fold expansion of functional, mature IL-10-competent regulatory spleen B cells (B10 cells: 26.7×106±6 in CD154TGCD22−/− mice; 1.7×106±0.4 in wild type mice, p<0.01), and an 11-fold expansion of B10 cells combined with their ex vivo-matured progenitors (B10+B10pro cells: 66×106±3 in CD154TGCD22−/− mice; 6.1×106±2 in wild type mice, p<0.01) that represented 39% of all spleen B cells.Conclusions/Significance
These results demonstrate for the first time that the IL-10-producing B10 B cell subset has the capacity to suppress IgG humoral immune responses against both foreign and self antigens. Thereby, therapeutic agents that drive regulatory B10 cell expansion in vivo may inhibit pathogenic IgG autoAb production in humans. 相似文献123.
Matsushita N Kitao H Ishiai M Nagashima N Hirano S Okawa K Ohta T Yu DS McHugh PJ Hickson ID Venkitaraman AR Kurumizaka H Takata M 《Molecular cell》2005,19(6):841-847
In DNA damage responses, the Fanconi anemia (FA) protein, FancD2, is targeted to chromatin and forms nuclear foci following its monoubiquitination, a process likely catalyzed by the FA core complex. Here, we show that a chicken FancD2-ubiquitin fusion protein, carrying a Lys-Arg substitution removing the natural monoubiquitination site (D2KR-Ub), could reverse cisplatin hypersensitivity and localize to chromatin in FANCD2-deficient DT40 cells. Importantly, the chromatin targeting was dependent on three core complex components as well as the hydrophobic surface of ubiquitin that may direct protein-protein interactions. Furthermore, a constitutively chromatin bound fusion of D2KR-histone H2B could complement cisplatin sensitivity in FANCD2- but not FANCC-, FANCG-, or FANCL-deficient cells. Thus these core complex components have an additional function in the DNA repair, which is independent of the monoubiquitination and chromatin targeting of FancD2. These results define functional consequences of FancD2 monoubiquitination and reveal previously hidden functions for the FA protein core complex. 相似文献
124.
Fujita Y Kasuya A Matsushita Y Suga M Kizuka M Iijima Y Ogita T 《Bioorganic & medicinal chemistry letters》2005,15(19):4317-4321
A-74528 (1) is a metabolite of Streptomyces sp. discovered in the screening for 2',5'-oligoadenylate phosphodiesterase inhibitors. The planar structure of 1 was mainly elucidated by NMR techniques including natural abundance INADEQUATE, and the relative configuration and the conformation were elucidated by the analyses of NOEs and assessment of dihedral angles predicted by QUANTA/CHARMm computations and coupling constants. It was proved that 1 is a highly fused polyketide with a side-chain branching site that never appeared before from the nature. 相似文献
125.
Nantapong N Otofuji A Migita CT Adachi O Toyama H Matsushita K 《Bioscience, biotechnology, and biochemistry》2005,69(1):149-159
Type II NADH dehydrogenase of Corynebacterium glutamicum (NDH-2) was purified from an ndh overexpressing strain. Purification conferred 6-fold higher specific activity of NADH:ubiquinone-1 oxidoreductase with a 3.5-fold higher recovery than that previously reported (K. Matsushita et al., 2000). UV-visible and fluorescence analyses of the purified enzyme showed that NDH-2 of C. glutamicum contained non-covalently bound FAD but not covalently bound FMN. This enzyme had an ability to catalyze electron transfer from NADH and NADPH to oxygen as well as various artificial quinone analogs at neutral and acidic pHs respectively. The reduction of native quinone of C. glutamicum, menaquinone-2, with this enzyme was observed only with NADH, whereas electron transfer to oxygen was observed more intensively with NADPH. This study provides evidence that C. glutamicum NDH-2 is a source of the reactive oxygen species, superoxide and hydrogen peroxide, concomitant with NADH and NADPH oxidation, but especially with NADPH oxidation. Together with this unique character of NADPH oxidation, phylogenetic analysis of NDH-2 from various organisms suggests that NDH-2 of C. glutamicum is more closely related to yeast or fungal enzymes than to other prokaryotic enzymes. 相似文献
126.
Fujita T Furukawa S Morita K Ishihara T Shiotani M Matsushita Y Matsuda M Shimomura I 《Biochemical and biophysical research communications》2005,328(2):369-374
Hyperglycemia-induced activation of hexosamine biosynthesis pathway (HBP) has been implicated in the development of insulin resistance in skeletal muscles. In the present study, the content of uridine-5'-diphospho-N-acetylglucosamine, the end product of the HBP, was elevated in skeletal muscle of obese diabetic KKA(y) mice, compared with control mice. To elucidate the effect of elevated HBP in the skeletal muscle, we treated C2C12 myoblasts with glucosamine, an intermediate metabolite of the HBP. Glucosamine induced lipid accumulation and significantly increased the mRNA expression levels of peroxisome proliferator-activated receptor gamma, adiponectin, and aP2 in C2C12 myoblasts. Similar mRNA changes were observed in skeletal muscles of Sprague-Dawley rats treated with glucosamine infusion. Our results provide a possible explanation of hyperglycemia-induced insulin resistance in skeletal muscle. 相似文献
127.
Human M-ficolin is a secretory protein that activates the lectin complement pathway 总被引:10,自引:0,他引:10
Liu Y Endo Y Iwaki D Nakata M Matsushita M Wada I Inoue K Munakata M Fujita T 《Journal of immunology (Baltimore, Md. : 1950)》2005,175(5):3150-3156
Three types of ficolins have been identified in humans: L-ficolin, M-ficolin, and H-ficolin. Similar to mannose-binding lectin, L-ficolin and H-ficolin are the recognition molecules in the lectin complement pathway. Another human ficolin, M-ficolin, is a nonserum ficolin that is expressed in leukocytes and lung; however, little is known about its physiologic roles. In this study, we report the characterization of M-ficolin in terms of its protein localization and lectin activity. M-ficolin was localized in secretory granules in the cytoplasm of neutrophils, monocytes, and type II alveolar epithelial cells in lung. M-ficolin precipitated with mannose-binding lectin-associated serine proteases (MASP)-1 and MASP-2 in a co-immunoprecipitation assay, indicating that M-ficolin forms complexes with MASP-1 and MASP-2. M-ficolin-MASP complexes activated complement on N-acetylglucosamine (GlcNAc)-coated microplates in a C4 deposition assay. M-ficolin bound to several neoglycoproteins bearing GlcNAc, N-acetylgalactosamine, and sialyl-N-acetyllactosamine, suggesting that M-ficolin can recognize the common carbohydrate residues found in microbes. Indeed, M-ficolin bound to Staphylococcus aureus through GlcNAc. These results indicate that M-ficolin, like its family members, functions as a recognition molecule of the lectin complement pathway and plays an important role in innate immunity. 相似文献
128.
The activity of the cerebral pyruvate recycling pathway and energy metabolism in mice infected with Trichinella spiralis were investigated using (13)C-NMR and in vivo (31)P-NMR spectroscopy, respectively. The (13)C-NMR analysis, using [1,2-(13)C(2)] acetate as a substrate, of whole-brain extracts demonstrated that activity of the pathway increased when T. spiralis infection induced hypoglycemia in the host. The in vivo (31)P-NMR observation showed that the cerebral ATP in normal level sustained throughout this experiment. These findings indicate that the pyruvate recycling pathway plays a role in the energy supply to the host in hypoglycemia induced by T. spiralis infection. 相似文献
129.
ACE1 polymorphism and progression of SARS 总被引:2,自引:0,他引:2
Itoyama S Keicho N Quy T Phi NC Long HT Ha LD Ban VV Ohashi J Hijikata M Matsushita I Kawana A Yanai H Kirikae T Kuratsuji T Sasazuki T 《Biochemical and biophysical research communications》2004,323(3):1124-1129
We have hypothesized that genetic predisposition influences the progression of SARS. Angiotensin converting enzyme (ACE1) insertion/deletion (I/D) polymorphism was previously reported to show association with the adult respiratory distress syndrome, which is also thought to play a key role in damaging the lung tissues in SARS cases. This time, the polymorphism was genotyped in 44 Vietnamese SARS cases, with 103 healthy controls who had had a contact with the SARS patients and 50 controls without any contact history. SARS cases were divided into either non-hypoxemic or hypoxemic groups. Despite the small sample size, the frequency of the D allele was significantly higher in the hypoxemic group than in the non-hypoxemic group (p=0.013), whereas there was no significant difference between the SARS cases and controls, irrespective of a contact history. ACE1 might be one of the candidate genes that influence the progression of pneumonia in SARS. 相似文献
130.