全文获取类型
收费全文 | 570篇 |
免费 | 48篇 |
专业分类
618篇 |
出版年
2023年 | 1篇 |
2022年 | 9篇 |
2021年 | 17篇 |
2020年 | 11篇 |
2019年 | 4篇 |
2018年 | 11篇 |
2017年 | 16篇 |
2016年 | 19篇 |
2015年 | 23篇 |
2014年 | 40篇 |
2013年 | 36篇 |
2012年 | 41篇 |
2011年 | 35篇 |
2010年 | 20篇 |
2009年 | 24篇 |
2008年 | 31篇 |
2007年 | 44篇 |
2006年 | 33篇 |
2005年 | 31篇 |
2004年 | 27篇 |
2003年 | 23篇 |
2002年 | 18篇 |
2001年 | 14篇 |
2000年 | 13篇 |
1999年 | 14篇 |
1998年 | 5篇 |
1997年 | 4篇 |
1996年 | 4篇 |
1994年 | 4篇 |
1993年 | 2篇 |
1992年 | 3篇 |
1991年 | 5篇 |
1990年 | 4篇 |
1989年 | 1篇 |
1988年 | 1篇 |
1987年 | 2篇 |
1986年 | 1篇 |
1985年 | 4篇 |
1984年 | 1篇 |
1983年 | 5篇 |
1982年 | 4篇 |
1981年 | 1篇 |
1980年 | 3篇 |
1979年 | 2篇 |
1978年 | 2篇 |
1977年 | 1篇 |
1972年 | 1篇 |
1971年 | 3篇 |
排序方式: 共有618条查询结果,搜索用时 0 毫秒
81.
This review summarizes recent work that focuses on the role of endogenous opioids (EOs) and opiate receptors in the control of food intake. Although the anorexic effect of opiate antagonists are now well accepted, the exact EO, site(s), and mechanism(s) of action remain to be established. However, accumulating evidence suggests that dynorphin, an endogenous ligand for kappa-type opiate receptors, is an important regulator (stimulant) of appetite. The roles of other EOs, such as beta-endorphin, are less clear. EOs appear to be involved in maintaining normal feeding behavior and are likely responsible for the overconsumption of fat in genetically obese and stressed subjects. Opiate antagonists block overconsumption of palatable foods, thus offering a promising approach to weight reduction for some overweight individuals. Anorexias may follow from a deficiency of kappa-type opioid activity, and surprisingly, can also result from excess opioid activity. Indeed, opiate antagonists of the mu type (naloxone) can enhance eating and weight gain in certain anorexic conditions. Therefore, it appears that excess opioid agonist activity may result in hyperphagia or anorexia (depending on the opiate receptor type). Finally, opiate antagonists may help normalize both types of pathological feeding states. 相似文献
82.
Comparative study of Helicobacter pylori eradication rates of concomitant therapy vs modified quadruple therapy comprising proton‐pump inhibitor,bismuth, amoxicillin,and metronidazole in Korea 下载免费PDF全文
83.
Temporal and spatial transcriptomic and microRNA dynamics of CAM photosynthesis in pineapple 下载免费PDF全文
84.
Crystal structure of heart 6‐phosphofructo‐2‐kinase/fructose‐2,6‐bisphosphatase (PFKFB2) and the inhibitory influence of citrate on substrate binding 下载免费PDF全文
Robert B. Crochet Jeong‐Do Kim Herie Lee Young‐Sun Yim Song‐Gun Kim David Neau Yong‐Hwan Lee 《Proteins》2017,85(1):117-124
The heart‐specific isoform of 6‐phosphofructo‐2‐kinase/fructose‐2,6‐bisphosphatase (PFKFB2) is an important regulator of glycolytic flux in cardiac cells. Here, we present the crystal structures of two PFKFB2 orthologues, human and bovine, at resolutions of 2.0 and 1.8 Å, respectively. Citrate, a TCA cycle intermediate and well‐known inhibitor of PFKFB2, co‐crystallized in the 2‐kinase domains of both orthologues, occupying the fructose‐6‐phosphate binding‐site and extending into the γ‐phosphate binding pocket of ATP. This steric and electrostatic occlusion of the γ‐phosphate site by citrate proved highly consequential to the binding of co‐complexed ATP analogues. The bovine structure, which co‐crystallized with ADP, closely resembled the overall structure of other PFKFB isoforms, with ADP mimicking the catalytic binding mode of ATP. The human structure, on the other hand, co‐complexed with AMPPNP, which, unlike ADP, contains a γ‐phosphate. The presence of this γ‐phosphate made adoption of the catalytic ATP binding mode impossible for AMPPNP, forcing the analogue to bind atypically with concomitant conformational changes to the ATP binding‐pocket. Inhibition kinetics were used to validate the structural observations, confirming citrate's inhibition mechanism as competitive for F6P and noncompetitive for ATP. Together, these structural and kinetic data establish a molecular basis for citrate's negative feed‐back loop of the glycolytic pathway via PFKFB2. Proteins 2016; 85:117–124. © 2016 Wiley Periodicals, Inc. 相似文献
85.
Use of glnQ as a Counterselectable Marker for Creation of Allelic Exchange Mutations in Group B Streptococci 总被引:1,自引:0,他引:1 下载免费PDF全文
Glen S. Tamura Debra S. Bratt Harry H. Yim Aphakorn Nittayajarn 《Applied microbiology》2005,71(1):587-590
Efficient allelic exchange mutagenesis in group B streptococci (GBS) has been hampered by the lack of a counterselectable marker system. Growth inhibition of GBS by the glutamine analog gamma-glutamyl hydrazide requires glnQ. We have used this phenomenon to create a counterselectable marker system for efficient selection of allelic exchange mutants in GBS. 相似文献
86.
Babita Paudel Hari Datta Bhattarai Jin Sung Lee Soon Gyu Hong Hyun Woung Shin Joung Han Yim 《Polar Biology》2008,31(5):605-608
Antioxidant agents prevent reactive oxygen species, which can cause degenerative diseases. Natural antioxidants are preferred
over many synthetic antioxidants, which can be toxic, for therapeutic applications. Five lichen species were collected from
King George Island, Antarctica. Antioxidant activities as assessed by DPPH (1,1-diphenyl-2-picrylhydrazyl) free radical and
ABTS•+ [2,2’-azinobis-(3-ethylbenzothiazoline-6-sulfonate)] radical scavenging capacities were determined and compared with those
of commercial standards BHA (butylated hydroxyanisole) and trolox [(±)-6-hydroxy-2,5,7,8-tetramethylchromane-2-carboxylic
acid]. The results indicated that two lichens exhibited comparatively high antioxidant activities with the remaining three
exhibiting less activity. The antioxidant activity was concentration-dependent. When compared, the antioxidant activity of
crude extracts from polar lichens to previously published data for tropical and temperate lichen species, we concluded that
lichens of Antarctic origin may be the potent sources of strong antioxidant agents. Such species should be explored as novel
sources of effective antioxidant metabolites. 相似文献
87.
The use of luxABCDE (lux) offers certain advantages over other reporters, such as: lacZ and xylE. It is real time and its signal generation is produced without the requirement for any additional substrates. In some bacteria such as Staphylococcus spp, light production by luciferase is restricted because of a limited availability of endogenous substrates such as fatty acid aldehyde. We describe the construction of promoterless-lux cloning vectors, pGYlux and pAmilux. S. aureus carrying B. subtilis xyl/tetO promoter fused to the lux genes of pGYlux gave up to a 2.5-fold enhancement of luminescence over S. aureus carrying the xyl/tetO promoter fused to lux genes of the previously published parent vector pAL2. Furthermore, pAmilux showed a 6-fold enhancement of lux expression when compared to pGYlux in S. aureus. This was achieved by cloning the constitutive ami promoter upstream of the luxCDE genes to increase endogenous fatty acid aldehyde production while maintaining its reporter functionality by fusing promoters to the luxAB genes. 相似文献
88.
89.
CRISPR-Cas9 Knockin Mice for Genome Editing and Cancer Modeling 总被引:2,自引:0,他引:2
Randall J. Platt Sidi Chen Yang Zhou Michael J. Yim Lukasz Swiech Hannah R. Kempton James E. Dahlman Oren Parnas Thomas M. Eisenhaure Marko Jovanovic Daniel B. Graham Siddharth Jhunjhunwala Matthias Heidenreich Ramnik J. Xavier Robert Langer Daniel G. Anderson Nir Hacohen Aviv Regev Guoping Feng Phillip A. Sharp Feng Zhang 《Cell》2014
90.
Protein p63 is a key regulator in cell proliferation and cell differentiation in stratified squamous epithelium. ΔNp63α is the most commonly expressed p63 isoform, which is often overexpressed in human tumor. In the present work we report the potential involvement of ΔNp63α in cell cycle regulation. ΔNp63α accumulated in mitotic cells but its expression decreased during mitotic exit. Moreover, ΔNp63α knockdown promoted mitotic exit. ΔNp63α shares a conserved destruction box (D-box) motif with other potential targets of the Anaphase-Promoting Complex/Cyclosome (APC/C). Overexpression of APC/C coactivator Cdh1 destabilized ΔNp63α. Our results suggest that ΔNp63α level is cell cycle-regulated and may play a role in the regulation of mitotic exit. 相似文献