全文获取类型
收费全文 | 185篇 |
免费 | 4篇 |
出版年
2024年 | 1篇 |
2023年 | 2篇 |
2021年 | 7篇 |
2020年 | 4篇 |
2019年 | 3篇 |
2018年 | 4篇 |
2017年 | 3篇 |
2016年 | 5篇 |
2015年 | 8篇 |
2014年 | 13篇 |
2013年 | 15篇 |
2012年 | 17篇 |
2011年 | 15篇 |
2010年 | 6篇 |
2009年 | 7篇 |
2008年 | 11篇 |
2007年 | 10篇 |
2006年 | 9篇 |
2005年 | 10篇 |
2004年 | 2篇 |
2003年 | 4篇 |
2002年 | 6篇 |
2001年 | 7篇 |
2000年 | 3篇 |
1999年 | 4篇 |
1997年 | 2篇 |
1994年 | 1篇 |
1988年 | 1篇 |
1987年 | 1篇 |
1985年 | 1篇 |
1984年 | 1篇 |
1983年 | 3篇 |
1979年 | 2篇 |
1973年 | 1篇 |
排序方式: 共有189条查询结果,搜索用时 15 毫秒
21.
The extraordinary recognition specificity of lectins for carbohydrate ligands appears to be violated as they also bind to porphyrins and other noncarbohydrate ligands. In this study, crystal structures of meso-tetrasulfonatophenylporphyrin (H(2)TPPS) bound to peanut agglutinin (PNA) in the presence and absence of lactose were determined. The binding of H(2)TPPS with PNA involved 11 molecules of H(2)TPPS in different supramolecular stacking arrangements associated with a tetramer of PNA in the crystals of the PNA-H(2)TPPS binary complex as well as the PNA-H(2)TPPS-lactose ternary complex. The ternary complex involved lactose binding only to two subunits of the PNA tetramer, which did not have porphyrin interacting in the vicinity of the carbohydrate-binding site. Comparison of the two structures highlighted the plasticity of the carbohydrate-binding site expressed in terms of the conformational change in lactose binding. The unusual quaternary structure of PNA, which results in exposed protein-protein interaction sites, might be responsible for the porphyrin binding. The association of porphyrin in diverse oligomeric stacking arrangements observed in the PNA-H(2)TPPS complex suggested the possibility of protein-porphyrin aggregation under abnormal physiological conditions. The structures described here provide a possible native conformation of the carbohydrate-binding site of PNA in the absence of the ligand, highlight mapping of the unsaturated binding surfaces of PNA using porphyrin interactions, indicate new leads toward possible application of this lectin in photodynamic therapy, and exhibit diverse modes of porphyrin-lectin interactions with implications to porphyria, a disease that results from abnormal accumulation of porphyrins. 相似文献
22.
The search for safer non-steroidal anti-inflammatory drugs (NSAIDs) continues with the failure of anticipated 'ideal' anti-inflammatory agents, the coxibs, on long-term usage. Increased gastric motility and acidity due to the free carboxy group are involved in the etiology of gastric toxicity, common to conventional NSAIDs. Keeping this fact in mind, it was planned to modify some of the conventional NSAIDs to amino-alcohol ester derivatives, which satisfied the structural requirements for these compounds to possess anticholinergic activity in the intact form. Besides blocking the acidic carboxylic group, incorporation of anticholinergic acivity in these molecules was expected to reduce the gastric toxicity by decreasing gastric acid secretion and motility. Synthesis and pharmacological evaluation of six different N,N-disubstituted amino-ethyl ester derivatives, structurally resembling the amino-alcohol ester class of anticholinergic agents, each for [1,1'-biphenyl]-4-acetic acid (3) and flurbiprofen (10), have been reported as potential substitutes for these NSAIDs, with improved therapeutic profile. All the ester derivatives were found to have sufficient chemical stability in buffers (pH 2.0 and 7.4), ensuring them to be absorbed as intact moieties from the gastrointestinal tract. A significant reduction in ulcerogenic potency in comparison to the parent drugs with a slightly higher anti-inflammatory potency suggests that the majority of these candidates have an improved therapeutic profile over their parent drugs. Hence, a promising novel approach, different from the conventional prodrug concept, has been successfully worked out to overcome the local gastric toxicity, yielding therapeutically better compounds for long-term oral anti-inflammatory therapy. 相似文献
23.
Leonardo Faoro Patrick A. Singleton Gustavo M. Cervantes Frances E. Lennon Nicholas W. Choong Rajani Kanteti Benjamin D. Ferguson Aliya N. Husain Maria S. Tretiakova Nithya Ramnath Everett E. Vokes Ravi Salgia 《The Journal of biological chemistry》2010,285(24):18575-18585
Non-small cell lung cancer (NSCLC) has a poor prognosis and improved therapies are needed. Expression of EphA2 is increased in NSCLC metastases. In this study, we investigated EphA2 mutations in NSCLC and examined molecular pathways involved in NSCLC. Tumor and cell line DNA was sequenced. One EphA2 mutation was modeled by expression in BEAS2B cells, and functional and biochemical studies were conducted. A G391R mutation was detected in H2170 and 2/28 squamous cell carcinoma patient samples. EphA2 G391R caused constitutive activation of EphA2 with increased phosphorylation of Src, cortactin, and p130Cas. Wild-type (WT) and G391R cells had 20 and 40% increased invasiveness; this was attenuated with knockdown of Src, cortactin, or p130Cas. WT and G391R cells demonstrated a 70% increase in focal adhesion area. Mammalian target of rapamycin (mTOR) phosphorylation was increased in G391R cells with increased survival (55%) compared with WT (30%) and had increased sensitivity to rapamycin. A recurrent EphA2 mutation is present in lung squamous cell carcinoma and increases tumor invasion and survival through activation of focal adhesions and actin cytoskeletal regulatory proteins as well as mTOR. Further study of EphA2 as a therapeutic target is warranted. 相似文献
24.
25.
26.
Predictive classification of major structural families and fold types of proteins is investigated deploying logistic regression. Only five to seven dimensional quantitative feature vector representations of tertiary structures are found adequate. Results for benchmark sample of non-homologous proteins from SCOP database are presented. Importance of this work as compared to homology modeling and best-known quantitative approaches is highlighted. 相似文献
27.
Myosin folding and assembly in striated muscle is mediated by the general chaperones Hsc70 and Hsp90 and a myosin specific co-chaperone, UNC45. Two UNC45 genes are found in vertebrates, including a striated muscle specific form, Unc45b. We have investigated the role of Unc45b in myosin folding. Epitope tagged murine Unc45b (Unc45b(Flag)) was expressed in muscle and non-muscle cells and bacteria, isolated and characterized. The protein is a soluble monomer in solution with a compact folded rod-shaped structure of approximately 19 nm length by electron microscopy. When over-expressed in striated muscle cells, Unc45b(Flag) fractionates as a cytosolic protein and isolates as a stable complex with Hsp90. Purified Unc45b(Flag) re-binds Hsp90 and forms a stable complex in solution. The endogenous Unc45b in muscle cell lysates is also found associated with Hsp90. The Unc45b(Flag)/Hsp90 complex binds the partially folded myosin motor domain when incubated with myosin subfragments synthesized in a reticulocyte lysate. This binding is independent of the myosin rod or light chains. Unc45b(Flag) does not bind native myosin subfragments consistent with a chaperone function. More importantly, Unc45b(Flag) enhances myosin motor domain folding during de novo motor domain synthesis indicating that it has a direct role in myosin maturation. Thus, mammalian Unc45b is a cytosolic protein that forms a stable complex with Hsp90, selectively binds the unfolded conformation of the myosin motor domain, and promotes motor domain folding. 相似文献
28.
Yuri T. Yamamoto Nirmala Rajbhandari Xiaohong Lin Ben A. Bergmann Yufuko Nishimura Anne-Marie Stomp 《In vitro cellular & developmental biology. Plant》2001,37(3):349-353
Summary We developed efficient genetic transformation protocols for two species of duckweed, Lemna gibba (G3) and Lemna minor (8627 and 8744), using Agrobacterium-mediated gene transfer. Partially differentiated nodules were co-cultivated with Agrobacterium tumefaciens harboring a binary vector containing β-glucuronidase and nptII expression cassettes. Transformed cells were selected and allowed to grow into nodules in the presence of kanamycin. Transgenic
duckweed fronds were regenerated from selected nodules. We demonstrated that transgenic duckweed could be regenerated within
3 mo. after Agrobacterium-mediated transformation of nodules. Furthermore, we developed a method for transforming L. minor 8627 in 6 wk. These transformation protocols will facilitate genetic engineering of duckweed, ideal plants for bioremediation
and large-scale industrial production of biomass and recombinant proteins. 相似文献
29.
Summary The majority of bamboos (Graminae) are arborescent and perennial. The erect stems (culms) of woody bamboos are useful for
a wide variety of purposes. Most bamboos flower only once at the end of very long vegetative growth phases and die afterwards.
Flowering in bamboos is thought to be under genetic control, occurring somewhat like an alarm clock, going off at a preset
time. The nature of this genetic clock and any interaction between the ‘internal clock’ and the environment are not yet known.
Because of this ‘peculiar’ flowering behavior, bamboo seeds are available only at very long intervals. Obtaining concurrent
flowering in two or more species (or varieties) in space and time is difficult, making perennial seed propagation and genetic
improvement by breeding nearly impossible. Besides, this peculiar flowering behavior of bamboos is also believed to have brought
the giant pandas to the verge of extinction. One of the spectacular developments in the area of bamboo genetic improvement
has been the precocious in vitro induction of flowering. By this method it has been possible to rapidly accelerate the reproductive
development (within 3–6 mo. versus 30–60 yr in nature). This has opened the possibility of perennial seed propagation and
hybridization. In vitro induction of flowering can be obtained by diverse methods which show some similarities and differences.
Induction of flowering is possible in cultures derived from both juvenile and mature explants. The proportion of seedlings
induced to flower is possibly influenced by genotypic variation, though the role of methods used cannot be ruled out. A cytokinin
or a shift in the auxin-cytokinin equilibrium is believed to bring about in vitro induction of flowering. The pH of the media
also has an influence. Induction of flowering and rhizogenesis is considered to be an antagonistic phenomenon in vitro. A
comparison between in vitro and in vivo flowering in Bambusa arundinacea has shown that though smaller, in vitro-induced florets are comparable to normal florets. There is reduced pollen fertility
and some impairment in pollen wall development. Biochemical studies on the in vitro-induced flowering in bamboos have shown
(1) selective expression of esterase and peroxidase isozymes during transition of nonembryogenic calluses to embryogenic calluses,
somatic embryo development, germination and subsequent flowering of somatic embryo derived shoots, and (2) minimal peroxidase
activity before rhizogenesis and induction of flowering in vitro. There are reports of published and comparable methods having
failed to induce flowering in vitro. 相似文献
30.
Adventitious shoot buds were induced from leaf and stem explants of Bacopa monnieri on Murashige and Skoog medium supplemented with benzyladenine or kinetin. The source of the explants as well as different
gelling agents in the medium were found to influence shoot induction and eventual shoot growth. The best response was obtained
in leaf explants taken from shoot cultures grown in medium supplemented with 2 μM benzyladenine and gelled with 0.2% gelrite. A transverse section of the leaf explant incubated in this medium showed several
shoot primordia emerging from the leaf surface. This system exhibited a potential for repeated harvesting of the shoots from
the original leaf explant as the latter continued to expand and regenerate new shoots, upon repeated periodical subculturing
onto fresh medium. However, the callusing response of the plant was very low. Qualitative TLC studies of the regenerated shoots
revealed a phytochemical profile similar to that of the field grown-plants.
Received: 20 March 1998 / Revision received: 1 December 1998 / Accepted: 12 December 1998 相似文献