全文获取类型
收费全文 | 3348篇 |
免费 | 183篇 |
国内免费 | 6篇 |
出版年
2023年 | 34篇 |
2022年 | 48篇 |
2021年 | 184篇 |
2020年 | 91篇 |
2019年 | 111篇 |
2018年 | 137篇 |
2017年 | 90篇 |
2016年 | 159篇 |
2015年 | 200篇 |
2014年 | 216篇 |
2013年 | 258篇 |
2012年 | 264篇 |
2011年 | 256篇 |
2010年 | 126篇 |
2009年 | 119篇 |
2008年 | 164篇 |
2007年 | 157篇 |
2006年 | 139篇 |
2005年 | 117篇 |
2004年 | 111篇 |
2003年 | 108篇 |
2002年 | 95篇 |
2001年 | 25篇 |
2000年 | 16篇 |
1999年 | 29篇 |
1998年 | 24篇 |
1997年 | 18篇 |
1996年 | 7篇 |
1995年 | 20篇 |
1994年 | 15篇 |
1993年 | 16篇 |
1992年 | 11篇 |
1991年 | 12篇 |
1990年 | 7篇 |
1989年 | 12篇 |
1987年 | 10篇 |
1986年 | 6篇 |
1985年 | 13篇 |
1984年 | 5篇 |
1983年 | 9篇 |
1982年 | 10篇 |
1981年 | 11篇 |
1980年 | 13篇 |
1979年 | 6篇 |
1978年 | 9篇 |
1977年 | 8篇 |
1976年 | 5篇 |
1975年 | 6篇 |
1974年 | 5篇 |
1966年 | 5篇 |
排序方式: 共有3537条查询结果,搜索用时 171 毫秒
11.
Catharine J. Collar Mohammed I. Al-Salabi Mhairi L. Stewart Michael P. Barrett W. David Wilson Harry P. de Koning 《The Journal of biological chemistry》2009,284(49):34028-34035
Transporters play a vital role in both the resistance mechanisms of existing drugs and effective targeting of their replacements. Melarsoprol and diamidine compounds similar to pentamidine and furamidine are primarily taken up by trypanosomes of the genus Trypanosoma brucei through the P2 aminopurine transporter. In standardized competition experiments with [3H]adenosine, P2 transporter inhibition constants (Ki) have been determined for a diverse dataset of adenosine analogs, diamidines, Food and Drug Administration-approved compounds and analogs thereof, and custom-designed trypanocidal compounds. Computational biology has been employed to investigate compound structure diversity in relation to P2 transporter interaction. These explorations have led to models for inhibition predictions of known and novel compounds to obtain information about the molecular basis for P2 transporter inhibition. A common pharmacophore for P2 transporter inhibition has been identified along with other key structural characteristics. Our model provides insight into P2 transporter interactions with known compounds and contributes to strategies for the design of novel antiparasitic compounds. This approach offers a quantitative and predictive tool for molecular recognition by specific transporters without the need for structural or even primary sequence information of the transport protein. 相似文献
12.
Arumugam Parthasarathy Venkatachalam Gopi Subramanian Umadevi Anoop Simna Mohammed Jainuddin Yousuf Sheik H. Divya Elangovan Vellaichamy 《Molecular and cellular biochemistry》2013,378(1-2):217-228
Cardiac hormone atrial natriuretic peptide (ANP) and its receptor natriuretic peptide receptor-A (NPR-A) system acts as an intrinsic negative regulator of abnormal extracellular matrix (ECM) remodeling in the heart. However, the underlying mechanism by which ANP/NPR-A system opposes the ECM remodeling in the diseased heart is not well understood. Here, we investigated the anti-fibrotic mechanism of ANP/NPR-A in fibrotic agonist Angiotensin- II (ANG II)-treated adult cardiac fibroblast (CF) cells. Normal and NPR-A-suppressed adult CF cells were treated with ANG II (10?7 M) in the presence and absence of ANP (10?8 M) for 24 h. Total collagen concentration, activity and expression of MMP-2 and MMP-9, and nuclear translocation of Nuclear factor-kappaB (NF-κB-p50) were studied. NPR-A-suppressed adult CF cells exhibited a more pronounced increase in collagen production, ROS generation, and NF-κB-p50 nuclear translocation as compared to adult CF cells treated with agonist alone. ANP co-treatment significantly reverses the agonist-induced above changes in normal adult CF cells, while it failed to reverse the agonist-induced collagen synthesis in the NPR-A-suppressed adult CF cells. The cGMP analog (8-bromo-cGMP) treatment significantly attenuated the agonist-induced collagen synthesis both in normal and NPR-A-suppressed adult cells. The results of this study suggest that ANP/NPR-A signaling system antagonizes the agonist-induced collagen synthesis via suppressing the activities of MMP-2, MMP-9, ROS generation, and NF-κB nuclear translocation mechanism. 相似文献
13.
14.
One of the main determinants of lung surfactant function is the complex interplay between its protein and lipid components. The lipid specificity of surfactant protein B (SP-B), however, and the protein's ability to selectively squeeze out lipids, has remained contradictory. In this work we present, for the first time to our knowledge, by means of time-of-flight secondary ion mass spectrometry chemical imaging, a direct evidence for colocalization of SP-B as well as its model peptide KL4 with negatively charged dipalmitoylphosphatidylglycerol under absolute calcium free conditions. Our results prove that protein/lipid localization depends on the miscibility of all surfactant components, which itself is influenced by subphase ionic conditions. In contrast to our earlier studies reporting SP-B/KL4 colocalization with zwitterionic dipalmitoylphosphatidylcholine, in the presence of even the smallest traces of calcium, we finally evidence an apparent reversal of protein/lipid mixing behavior upon calcium removal with ethylene diamine tetraacetic acid. In addition, scanning force microscopy measurements reveal that by depleting the subphase from calcium ions the protrusion formation ability of SP-B or KL4 is not hampered. However, in the case of KL4, distinct differences in protrusion morphology and height are visible. Our results support the idea that calcium ions act as a “miscibility switch” in surfactant model systems and probably are one of the major factors steering lipid/protein mixing behavior as well as influencing the protein's protrusion formation ability. 相似文献
15.
16.
17.
18.
Lucia Romani Josefa Koroivueta Andrew C. Steer Mike Kama John M. Kaldor Handan Wand Mohammed Hamid Margot J. Whitfeld 《PLoS neglected tropical diseases》2015,9(3)
BackgroundScabies is recognised as a major public health problem in many countries, and is responsible for significant morbidity due to secondary bacterial infection of the skin causing impetigo, abscesses and cellulitis, that can in turn lead to serious systemic complications such as septicaemia, kidney disease and, potentially, rheumatic heart disease. Despite the apparent burden of disease in many countries, there have been few large-scale surveys of scabies prevalence or risk factors. We undertook a population-based survey in Fiji of scabies and impetigo to evaluate the magnitude of the problem and inform public health strategies.ConclusionsAs far as we are aware, this is the first national survey of scabies and impetigo ever conducted. We found that scabies occurs at high levels across all age groups, ethnicities, and geographical locations. Improved strategies are urgently needed to achieve control of scabies and its complications in endemic communities. 相似文献
19.
20.