全文获取类型
收费全文 | 1882篇 |
免费 | 144篇 |
国内免费 | 94篇 |
出版年
2023年 | 15篇 |
2022年 | 67篇 |
2021年 | 89篇 |
2020年 | 44篇 |
2019年 | 85篇 |
2018年 | 85篇 |
2017年 | 62篇 |
2016年 | 69篇 |
2015年 | 87篇 |
2014年 | 115篇 |
2013年 | 116篇 |
2012年 | 166篇 |
2011年 | 132篇 |
2010年 | 104篇 |
2009年 | 74篇 |
2008年 | 83篇 |
2007年 | 71篇 |
2006年 | 80篇 |
2005年 | 58篇 |
2004年 | 44篇 |
2003年 | 52篇 |
2002年 | 51篇 |
2001年 | 38篇 |
2000年 | 38篇 |
1999年 | 36篇 |
1998年 | 16篇 |
1997年 | 23篇 |
1996年 | 16篇 |
1995年 | 18篇 |
1994年 | 14篇 |
1993年 | 14篇 |
1992年 | 19篇 |
1991年 | 28篇 |
1990年 | 12篇 |
1989年 | 13篇 |
1988年 | 5篇 |
1987年 | 14篇 |
1986年 | 6篇 |
1985年 | 6篇 |
1983年 | 4篇 |
1982年 | 4篇 |
1981年 | 3篇 |
1980年 | 4篇 |
1979年 | 3篇 |
1978年 | 3篇 |
1975年 | 3篇 |
1974年 | 4篇 |
1973年 | 4篇 |
1971年 | 4篇 |
1967年 | 3篇 |
排序方式: 共有2120条查询结果,搜索用时 31 毫秒
141.
Li Liu Jingang Cui Qinbo Yang Chenglin Jia Minqi Xiong Bingbing Ning Xiaoye Du Peiwei Wang Xintong Yu Li Li Wenjian Wang Yu Chen Teng Zhang 《Biochemical and biophysical research communications》2014
Oxidative stress is mechanistically implicated in the pathogenesis of myocardial injury and the subsequent fibrogenic tissue remodeling. Therapies targeting oxidative stress in the process of myocardial fibrogenesis are still lacking and thus remain as an active research area in myocardial injury management. The current study evaluated the effects of a NADPH oxidase inhibitor, apocynin, on the production of reactive oxygen species and the development of myocardial fibrogenesis in isoproterenol (ISO)-induced myocardial injury mouse model. The results revealed a remarkable effect of apocynin on attenuating the development of myocardial necrotic lesions, inflammation and fibrogenesis. Additionally, the protective effects of apocynin against myocardial injuries were associated with suppressed expression of an array of genes implicated in inflammatory and fibrogenic responses. Our study thus provided for the first time the histopathological and molecular evidence supporting the therapeutic value of apocynin against the development of myocardial injuries, in particular, myocardial fibrogenesis, which will benefit the mechanism-based drug development targeting oxidative stress in preventing and/or treating related myocardial disorders. 相似文献
142.
Ming Chen Rui Wang Xi Gan Aiying Lei Chao Li Xiaoli Yu Jun Huang Ting Huang Wanwen Liang 《Molecular biology reports》2010,37(5):2541-2547
Suppression subtractive hybridization library was generated by comparison of cDNA populations isolated from peripheral leukocytes
of pre- and post-immunized tilapia. One cDNA sequence encoding complete inducible cAMP early repressor was obtained from the
library. The sequence was characterized by the presence of the basic structure of ICER IIγ. Expression of ICER was in the
tissues of four types of tilapia was decreased after infection with Streptococcus. After immunization, expression of ICER was initially decreased and then increased after 7 days. In addition, the order for
the overall expression of ICER gene after infection and the increases of ICER expression later after immunization in these
four types of tilapia was positively correlated to the disease resistance and productivity of these four species of tilapia.
Our results provided molecular mechanisms for the different disease resistance capability in different species of tilapia.
In addition, our results also provided reference molecular marker for breeding disease resistant tilapia, cAMP responsive
element modulator. 相似文献
143.
Internalization of Flax Rust Avirulence Proteins into Flax and Tobacco Cells Can Occur in the Absence of the Pathogen 总被引:1,自引:0,他引:1
Maryam Rafiqi Pamela H.P. Gan Michael Ravensdale Gregory J. Lawrence Jeffrey G. Ellis David A. Jones Adrienne R. Hardham Peter N. Dodds 《The Plant cell》2010,22(6):2017-2032
Translocation of pathogen effector proteins into the host cell cytoplasm is a key determinant for the pathogenicity of many bacterial and oomycete plant pathogens. A number of secreted fungal avirulence (Avr) proteins are also inferred to be delivered into host cells, based on their intracellular recognition by host resistance proteins, including those of flax rust (Melampsora lini). Here, we show by immunolocalization that the flax rust AvrM protein is secreted from haustoria during infection and accumulates in the haustorial wall. Five days after inoculation, the AvrM protein was also detected within the cytoplasm of a proportion of plant cells containing haustoria, confirming its delivery into host cells during infection. Transient expression of secreted AvrL567 and AvrM proteins fused to cerulean fluorescent protein in tobacco (Nicotiana tabacum) and flax cells resulted in intracellular accumulation of the fusion proteins. The rust Avr protein signal peptides were functional in plants and efficiently directed fused cerulean into the secretory pathway. Thus, these secreted effectors are internalized into the plant cell cytosol in the absence of the pathogen, suggesting that they do not require a pathogen-encoded transport mechanism. Uptake of these proteins is dependent on signals in their N-terminal regions, but the primary sequence features of these uptake regions are not conserved between different rust effectors. 相似文献
144.
Mattan Hurevich Yftah Tal‐Gan Shoshana Klein Yaniv Barda Alexander Levitzki Chaim Gilon 《Journal of peptide science》2010,16(4):178-185
Cyclization of bioactive peptides, utilizing functional groups serving as natural pharmacophors, is often accompanied with loss of activity. The backbone cyclization approach was developed to overcome this limitation and enhance pharmacological properties. Backbone cyclic peptides are prepared by the incorporation of special building units, capable of forming amide, disulfide and coordinative bonds. Urea bridge is often used for the preparation of cyclic peptides by connecting two amine functionalized side chains. Here we present urea backbone cyclization as an additional method for the preparation of backbone cyclic peptide libraries. A straightforward method for the synthesis of crystalline Fmoc‐Nα [ω‐amino(Alloc)‐alkyl] glycine building units is presented. A set of urea backbone cyclic Glycogen Synthase Kinase 3 analogs was prepared and assessed for protein kinase B inhibition as anticancer leads. Copyright © 2010 European Peptide Society and John Wiley & Sons, Ltd. 相似文献
145.
146.
Germ cells and somatic cells have the identical genome. However, unlike the mortal fate of somatic cells, germ cells have the unique ability to differentiate into gametes that retain totipotency and produce an entire organism upon fertilization. The processes by which germ cells differentiate into gametes, and those by which gametes become embryos, involve dramatic cellular differentiation accompanied by drastic changes in gene expression, which are tightly regulated by genetic circuitries as well as epigenetic mechanisms. Epigenetic regulation refers to heritable changes in gene expression that are not due to changes in primary DNA sequence. The past decade has witnessed an ever-increasing understanding of epigenetic regulation in many different cell types/tissues during embryonic development and adult homeostasis. In this review, we focus on recent discoveries of epigenetic regulation of germ cell differentiation in various metazoan model organisms, including worms, flies, and mammals. 相似文献
147.
Fei-Fei Zhang Lin-Ling Gan Cheng-He Zhou 《Bioorganic & medicinal chemistry letters》2010,20(6):1881-1884
A series of N-substituted carbazole derivatives were synthesized and evaluated for antibacterial and antifungal activities against Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRSA), Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa, Bacillus proteus, Candida albicans and Aspergillus fumigatus by two fold serial dilution technique. Some of the synthesized compounds displayed comparable or even better antibacterial and antifungal activities than reference drugs fluconazole, chloramphenicol and norfloxacin against tested strains. 相似文献
148.
Tricyclic dihydroquinazolinones as novel 5-HT2C selective and orally efficacious anti-obesity agents
Saleem Ahmad Khehyong Ngu Keith J. Miller Ginger Wu Chen-pin Hung Sarah Malmstrom Ge Zhang Eva O’Tanyi William J. Keim Mary Jane Cullen Kenneth W. Rohrbach Michael Thomas Thao Ung Qinling Qu Jinping Gan Rangaraj Narayanan Mary Ann Pelleymounter Jeffrey A. Robl 《Bioorganic & medicinal chemistry letters》2010,20(3):1128-1133
Agonists of the 5-HT2C receptor have been shown to suppress appetite and reduce body weight in animal models as well as in humans. However, agonism of the related 5-HT2B receptor has been associated with valvular heart disease. Synthesis and biological evaluation of a series of novel and highly selective dihydroquinazolinone-derived 5-HT2C agonists with no detectable agonism of the 5-HT2B receptor is described. Among these, compounds (+)-2a and (+)-3c were identified as potent and highly selective agonists which exhibited weight loss in a rat model upon oral dosing. 相似文献
149.
Li X Er MJ Lim BS Zhou JH Gan OP Rutkowski L 《International journal of neural systems》2010,20(5):405-419
In this paper, the viability of using Fuzzy-Rule-Based Regression Modeling (FRM) algorithm for tool performance and degradation detection is investigated. The FRM is developed based on a multi-layered fuzzy-rule-based hybrid system with Multiple Regression Models (MRM) embedded into a fuzzy logic inference engine that employs Self Organizing Maps (SOM) for clustering. The FRM converts a complex nonlinear problem to a simplified linear format in order to further increase the accuracy in prediction and rate of convergence. The efficacy of the proposed FRM is tested through a case study - namely to predict the remaining useful life of a ball nose milling cutter during a dry machining process of hardened tool steel with a hardness of 52-54 HRc. A comparative study is further made between four predictive models using the same set of experimental data. It is shown that the FRM is superior as compared with conventional MRM, Back Propagation Neural Networks (BPNN) and Radial Basis Function Networks (RBFN) in terms of prediction accuracy and learning speed. 相似文献
150.
Deng Li Qingfeng He Tao Kang Huan Yin Xian Jin Weiqiong Gan Jingjing Hu Lifei Peng 《Biochemical and biophysical research communications》2010,392(2):155-159
Factor VIIa-tissue factor complex (fVIIa/TF) and factor XIa (fXIa) play important roles in the initiation and amplification of coagulation, respectively. They may be good targets for the development of novel anticoagulants to treat and prevent thromboembolic disease. In this study, we cloned, expressed and identified a novel anticoagulant peptide, AcaNAP10, from the blood-feeding nematode Ancylostoma caninum. AcaNAP10 showed potent anticoagulant activity and doubled the activated partial thromboplastin and prothrombin times at estimated concentrations of 92.9 nM and 28.8 nM, respectively. AcaNAP10 demonstrated distinct mechanisms of action compared with known anticoagulants. It inhibited fXIa and fVIIa/TF with IC50 values of 25.76 ± 1.06 nM and 123.9 ± 1.71 nM, respectively. This is the first report on an anticoagulant that can inhibit both fXIa and fVIIa/TF. This anticoagulant peptide may be an alternative molecule for the development of novel anticoagulants. 相似文献