全文获取类型
收费全文 | 2158篇 |
免费 | 103篇 |
国内免费 | 212篇 |
专业分类
2473篇 |
出版年
2024年 | 3篇 |
2023年 | 20篇 |
2022年 | 47篇 |
2021年 | 60篇 |
2020年 | 69篇 |
2019年 | 76篇 |
2018年 | 79篇 |
2017年 | 71篇 |
2016年 | 65篇 |
2015年 | 60篇 |
2014年 | 124篇 |
2013年 | 134篇 |
2012年 | 72篇 |
2011年 | 116篇 |
2010年 | 72篇 |
2009年 | 136篇 |
2008年 | 156篇 |
2007年 | 137篇 |
2006年 | 117篇 |
2005年 | 113篇 |
2004年 | 77篇 |
2003年 | 65篇 |
2002年 | 60篇 |
2001年 | 36篇 |
2000年 | 39篇 |
1999年 | 58篇 |
1998年 | 47篇 |
1997年 | 46篇 |
1996年 | 29篇 |
1995年 | 30篇 |
1994年 | 42篇 |
1993年 | 26篇 |
1992年 | 28篇 |
1991年 | 21篇 |
1990年 | 17篇 |
1989年 | 17篇 |
1988年 | 20篇 |
1987年 | 9篇 |
1986年 | 12篇 |
1985年 | 6篇 |
1984年 | 11篇 |
1983年 | 7篇 |
1982年 | 4篇 |
1981年 | 6篇 |
1980年 | 5篇 |
1979年 | 4篇 |
1978年 | 3篇 |
1973年 | 4篇 |
1965年 | 2篇 |
1953年 | 2篇 |
排序方式: 共有2473条查询结果,搜索用时 15 毫秒
31.
JÜRG GERTSCH STEFAN RADUNER KARL-HEINZ ALTMANN 《Journal of receptor and signal transduction research》2013,33(5-6):709-730
Since the discovery that Δ 9-tetrahydrocannabinol and related cannabinoids from Cannabis sativa L. act on specific physiological receptors in the human body and the subsequent elucidation of the mammalian endogenous cannabinoid system, no other natural product class has been reported to mimic the effects of cannabinoids. We recently found that N-alkyl amides from purple coneflower (Echinacea spp.) constitute a new class of cannabinomimetics, which specifically engage and activate the cannabinoid type-2 (CB2) receptors. Cannabinoid type-1 (CB1) and CB2 receptors belong to the family of G protein-coupled receptors and are the primary targets of the endogenous cannabinoids N-arachidonoyl ethanolamine and 2-arachidonoyl glyerol. CB2 receptors are believed to play an important role in distinct pathophysiological processes, including metabolic dysregulation, inflammation, pain, and bone loss. CB2 receptors have, therefore, become of interest as new targets in drug discovery. This review focuses on N-alkyl amide secondary metabolites from plants and underscores that this group of compounds may provide novel lead structures for the development of CB2-directed drugs. 相似文献
32.
R. D. Ellender F. Morton J. Whelan B. H. Sweet 《Preparative biochemistry & biotechnology》2013,43(3):215-228
The ability of the Canalco Model CF-3 electro-osmosis (EO) apparatus to concentrate viruses from artificially seeded distilled water was improved. Modification of the physical arrangement of the equipment allowed for a 10–25 fold increase in concentration efficiency and a concomitant decrease in the process time. The major improvements involved modifications of the cell arrangement (which increased the membrane transport area), a change in the salt replenishing solution and the use of different membranes of higher flux. Viruses concentrated by E0 from seeded tap water resulted in lower recoveries when compared to distilled water. The lower yields were probably due to instability or aggregation of the agents in the menstruum and not directly related to the physical apparatus. Under the conditions used, one could detect virus at levels as low as 0.01 plaque forming units (PFU) per ml of initial input. The efficacy of a modification of the Canalco forced-flow electrophoretic (FFE) system was also evaluated. The maximum potential was applied with a constant value for pump rates. A 6-fold concentration of virus and a 12-fold decrease in water volume was obtained. 相似文献
33.
34.
Background
Biomedical data available to researchers and clinicians have increased dramatically over the past years because of the exponential growth of knowledge in medical biology. It is difficult for curators to go through all of the unstructured documents so as to curate the information to the database. Associating genes with diseases is important because it is a fundamental challenge in human health with applications to understanding disease properties and developing new techniques for prevention, diagnosis and therapy.Methods
Our study uses the automatic rule-learning approach to gene–disease relationship extraction. We first prepare the experimental corpus from MEDLINE and OMIM. A parser is applied to produce some grammatical information. We then learn all possible rules that discriminate relevant from irrelevant sentences. After that, we compute the scores of the learned rules in order to select rules of interest. As a result, a set of rules is generated.Results
We produce the learned rules automatically from the 1000 positive and 1000 negative sentences. The test set includes 400 sentences composed of 200 positives and 200 negatives. Precision, recall and F-score served as our evaluation metrics. The results reveal that the maximal precision rate is 77.8% and the maximal recall rate is 63.5%. The maximal F-score is 66.9% where the precision rate is 70.6% and the recall rate is 63.5%.Conclusions
We employ the rule-learning approach to extract gene–disease relationships. Our main contributions are to build rules automatically and to support a more complete set of rules than a manually generated one. The experiments show exhilarating results and some improving efforts will be made in the future. 相似文献35.
Faizul Azam Honiwa Suliman Abodabos Ismail M. Taban Abdalla R. Rfieda Danish Mahmood Md Jamir Anwar 《Molecular simulation》2013,39(18):1563-1571
ABSTRACTInhibitors of monoamine oxidase (MAO)-B have been used for many years in the therapy of Parkinson’s disease (PD). Owing to the safety concerns of the currently used agents, the discovery of novel scaffolds is of considerable interest. MAO-B inhibitory potential of rutin, a flavonoid derived from natural sources, has been established in experimental findings. Hence, the current study seeks to examine the interactions between rutin and crystal structure of human MAO-B enzyme. Molecular docking calculations, as well as molecular dynamics simulations, were employed to investigate the binding mode and the stability of the rutin/MAO-B complex. Energies of highest occupied/lowest unoccupied molecular orbitals were computed through DFT studies and used to calculate electron affinity, hardness, chemical potential, electronegativity, and electrophilicity index in order to investigate the capability of these parameters to influence the ligand–receptor interactions. It was found that rutin traverses both the entrance cavity and the substrate cavity, forcing the Ile-199 ‘gate’ to rotate into its open conformation. It results in the fusion of the two cavities of the MAO-B binding site and directly leads to better binding interactions. Results of the current study can be used for lead modification and development of novel drugs for the treatment of PD. 相似文献
36.
The use of a Monte–Carlo formalism in a centrifugal gas process separation simulation provides an efficient predictor of dew-pointing as a function of the imposed radial pressure gradient. Previously, this was done by simply calculating radial pressure and then resorting to a separate equation of state routine for evaluating whether condensation will occur or not. In our model, we incorporate the potential energy associated with rotation of a gas element into the simulation along with molecular interaction terms. This enables us to predict when sufficient nucleation has occurred that condensed material forms—an important limit for stable operation of a gas centrifuge. 相似文献
37.
Frank Scherbarth 《Chronobiology international》2013,30(6):905-922
Djungarian hamsters (Phodopus sungorus) exhibit pronounced winter acclimatization with changes in body mass, gonads, fur, and thermogenic capacity induced by decreasing daylength. To determine whether the annual activity pattern reflects the crucial role of the photoperiod for the hamsters' seasonality, animals with and without access to a running wheel (RW) were exposed to natural lighting conditions (~52°N) and ambient temperatures. Registration of locomotion in hamsters with a RW revealed a clear activity pattern closely related to dusk and dawn throughout the year. In contrast, animals without RW access showed a less stable phase relationship between the activity and the day‐night cycle in autumn and winter. During these seasons, the activity phase either exceeded the dark phase or even became indistinguishable from the rest phase. This correlated not only with increased locomotion during the light phase but also over the whole 24 h period, especially in autumn. In RW hamsters, a similar but attenuated trend was found that possibly reflects foraging due to increased food hoarding before winter. The more stable correlation between activity time and night length in RW hamsters might be explained by a suppressing effect of light on wheel‐running behavior (negative masking) and/or a stabilizing effect of running exercise on rhythmicity. In a further experiment, the phase‐reference points lights‐off and lights‐on within artificial light‐dark (LD) cycles were compared to sunset and sunrise in an intermediate ratio of light and dark and in long days. With respect to the defined phase‐reference points of the zeitgeber, the phase relation between activity and the LD cycle was similar in natural and corresponding artificial lighting conditions, and dependent on the LD ratio. 相似文献
38.
JiHoon Kang EunGi Kim Wanyeon Kim Ki Moon Seong HyeSook Youn Jung Woo Kim Joon Kim BuHyun Youn 《The Journal of biological chemistry》2013,288(38):27343-27357
Radioresistance is a major cause of decreasing the efficiency of radiotherapy for non-small cell lung cancer (NSCLC). To understand the radioresistance mechanisms in NSCLC, we focused on the radiation-induced Notch-1 signaling pathway involved in critical cell fate decisions by modulating cell proliferation. In this study, we investigated the use of Notch-1-regulating flavonoid compounds as novel therapeutic drugs to regulate radiosensitivity in NSCLC cells, NCI-H1299 and NCI-H460, with different levels of radioresistance. Rhamnetin and cirsiliol were selected as candidate Notch-1-regulating radiosensitizers based on the results of assay screening for activity and pharmacological properties. Treatment with rhamnetin or cirsiliol reduced the proliferation of NSCLC cells through the suppression of radiation-induced Notch-1 expression. Indeed, rhamnetin and cirsiliol increased the expression of tumor-suppressive microRNA, miR-34a, in a p53-dependent manner, leading to inhibition of Notch-1 expression. Consequently, reduced Notch-1 expression promoted apoptosis through significant down-regulation of the nuclear factor-κB pathway, resulting in a radiosensitizing effect on NSCLC cells. Irradiation-induced epithelial-mesenchymal transition was also notably attenuated in the presence of rhamnetin and cirsiliol. Moreover, an in vivo xenograft mouse model confirmed the radiosensitizing and epithelial-mesenchymal transition inhibition effects of rhamnetin and cirsiliol we observed in vitro. In these mice, tumor volume was significantly reduced by combinational treatment with irradiation and rhamnetin or cirsiliol compared with irradiation alone. Taken together, our findings provided evidence that rhamnetin and cirsiliol can act as promising radiosensitizers that enhance the radiotherapeutic efficacy by inhibiting radiation-induced Notch-1 signaling associated with radioresistance possibly via miR-34a-mediated pathways. 相似文献
39.
Marco I. Ries Hazrat Ali Peter P. Lankhorst Thomas Hankemeier Roel A. L. Bovenberg Arnold J. M. Driessen Rob J. Vreeken 《The Journal of biological chemistry》2013,288(52):37289-37295
Metabolic profiling and structural elucidation of novel secondary metabolites obtained from derived deletion strains of the filamentous fungus Penicillium chrysogenum were used to reassign various previously ascribed synthetase genes of the roquefortine/meleagrin pathway to their corresponding products. Next to the structural characterization of roquefortine F and neoxaline, which are for the first time reported for P. chrysogenum, we identified the novel metabolite roquefortine L, including its degradation products, harboring remarkable chemical structures. Their biosynthesis is discussed, questioning the exclusive role of glandicoline A as key intermediate in the pathway. The results reveal that further enzymes of this pathway are rather unspecific and catalyze more than one reaction, leading to excessive branching in the pathway with meleagrin and neoxaline as end products of two branches. 相似文献
40.
Xianwen Cao Jing Jiang Shoude Zhang Lili Zhu Juan Zou Yanyan Diao Weilie Xiao Lei Shan Handong Sun Weidong Zhang Jin Huang Honglin Li 《Bioorganic & medicinal chemistry letters》2013,23(11):3329-3333
Eleven compounds were identified as estrogen receptor modulators from an in-house natural product database (NPD) by structure-based virtual screening for ERα and ERβ. Among them, 3 compounds were confirmed as ER agonists and 8 compounds were confirmed as ER antagonists by yeast two-hybrid (Y2H) assay, with EC50 values ranging from several micromolar to 100 micromolar. In this study, a novel series of cycloartane triterpenoids isolated from Schisandra glaucescens Diels was found to have ER antagonistic effect, the most potent antagonist of which exhibited activity with EC50 value of 2.55 and 4.68 μM for ERα and ERβ, respectively. Moreover, the types of modulation and subtype selectivity were also investigated through molecular docking simulation. 相似文献