全文获取类型
收费全文 | 222篇 |
免费 | 18篇 |
专业分类
240篇 |
出版年
2022年 | 1篇 |
2021年 | 6篇 |
2020年 | 3篇 |
2019年 | 3篇 |
2018年 | 3篇 |
2017年 | 4篇 |
2016年 | 3篇 |
2015年 | 6篇 |
2014年 | 7篇 |
2013年 | 11篇 |
2012年 | 20篇 |
2011年 | 13篇 |
2010年 | 12篇 |
2009年 | 10篇 |
2008年 | 7篇 |
2007年 | 17篇 |
2006年 | 17篇 |
2005年 | 14篇 |
2004年 | 8篇 |
2003年 | 10篇 |
2002年 | 13篇 |
1999年 | 1篇 |
1998年 | 2篇 |
1997年 | 3篇 |
1996年 | 4篇 |
1995年 | 1篇 |
1994年 | 3篇 |
1993年 | 1篇 |
1992年 | 2篇 |
1991年 | 1篇 |
1990年 | 1篇 |
1989年 | 1篇 |
1988年 | 1篇 |
1987年 | 2篇 |
1986年 | 1篇 |
1985年 | 1篇 |
1982年 | 5篇 |
1981年 | 3篇 |
1980年 | 1篇 |
1979年 | 3篇 |
1978年 | 3篇 |
1976年 | 2篇 |
1975年 | 2篇 |
1973年 | 1篇 |
1971年 | 1篇 |
1970年 | 1篇 |
1968年 | 1篇 |
1967年 | 2篇 |
1966年 | 2篇 |
排序方式: 共有240条查询结果,搜索用时 0 毫秒
51.
The surface of a protein, or a membrane, is spotted with a multitude of proton binding sites, some of which are only few Å apart. When a proton is released from one site, it propagates through the water by a random walk under the bias of the local electrostatic potential determined by the distribution of the charges on the protein. Eventually, the released protons are dispersed in the bulk, but during the first few nanoseconds after the dissociation, the protons can be trapped by encounter with nearby acceptor sites. While the study of this reaction on the surface of a protein suffers from experimental and theoretical difficulties, it can be investigated with simple model compounds like derivatives of fluorescein. In the present study, we evaluate the mechanism of proton transfer reactions that proceed, preferentially, inside the Coulomb cage of the dye molecules. Kinetic analysis of the measured dynamics reveals the role of the dimension of the Coulomb cage on the efficiency of the reaction and how the ordering of the water molecules by the dye affects the kinetic isotope effect. 相似文献
52.
The surface of a protein, or a membrane, is spotted with a multitude of proton binding sites, some of which are only few A apart. When a proton is released from one site, it propagates through the water by a random walk under the bias of the local electrostatic potential determined by the distribution of the charges on the protein. Eventually, the released protons are dispersed in the bulk, but during the first few nanoseconds after the dissociation, the protons can be trapped by encounter with nearby acceptor sites. While the study of this reaction on the surface of a protein suffers from experimental and theoretical difficulties, it can be investigated with simple model compounds like derivatives of fluorescein. In the present study, we evaluate the mechanism of proton transfer reactions that proceed, preferentially, inside the Coulomb cage of the dye molecules. Kinetic analysis of the measured dynamics reveals the role of the dimension of the Coulomb cage on the efficiency of the reaction and how the ordering of the water molecules by the dye affects the kinetic isotope effect. 相似文献
53.
Inbar Maymon Yaarit Greenboim-Wainberg Sivan Sagiv Joseph J. Kieber Menachem Moshelion Neil Olszewski David Weiss 《The Plant journal : for cell and molecular biology》2009,58(6):979-988
Specific plant developmental processes are modulated by cross-talk between gibberellin (GA)- and cytokinin-response pathways. Coordination of the two pathways involves the O-linked N -acetylglucosamine transferase SPINDLY (SPY) that suppresses GA signaling and promotes cytokinin responses in Arabidopsis. Although SPY is a nucleocytoplasmic protein, its site of action and targets are unknown. Several studies have suggested that SPY acts in the nucleus, where it modifies nuclear components such as the DELLA proteins to regulate signaling networks. Using chimeric GFP–SPY fused to a nuclear-export signal or to a glucocorticoid receptor, we show that cytosolic SPY promotes cytokinin responses and suppresses GA signaling. In contrast, nuclear-localized GFP–SPY failed to complement the spy mutation. To examine whether modulation of cytokinin activity by GA and spy is mediated by the nuclear DELLA proteins, cytokinin responses were studied in double and quadruple della mutants lacking the activities of REPRESSOR OF GA1-3 (RGA) and GA-INSENSITIVE (GAI) or RGA, GAI, RGA Like1 (RGL1) and RGL2. Unlike spy , the della mutants were cytokinin-sensitive. Moreover, when GA was applied to a cytokinin-treated quadruple della mutant it was able to suppress various cytokinin responses. These results suggest that cytosolic SPY and GA regulate cytokinin responses via a DELLA-independent pathway(s). 相似文献
54.
Viruses differ markedly in their specificity toward host organisms. Here, we test the level of general sequence adaptation that viruses display toward their hosts. We compiled a representative data set of viruses that infect hosts ranging from bacteria to humans. We consider their respective amino acid and codon usages and compare them among the viruses and their hosts. We show that bacteria‐infecting viruses are strongly adapted to their specific hosts, but that they differ from other unrelated bacterial hosts. Viruses that infect humans, but not those that infect other mammals or aves, show a strong resemblance to most mammalian and avian hosts, in terms of both amino acid and codon preferences. In groups of viruses that infect humans or other mammals, the highest observed level of adaptation of viral proteins to host codon usages is for those proteins that appear abundantly in the virion. In contrast, proteins that are known to participate in host‐specific recognition do not necessarily adapt to their respective hosts. The implication for the potential of viral infectivity is discussed. 相似文献
55.
56.
In nature, proteins partake in numerous protein– protein interactions that mediate their functions. Moreover, proteins have been shown to be physically stable in multiple structures, induced by cellular conditions, small ligands, or covalent modifications. Understanding how protein sequences achieve this structural promiscuity at the atomic level is a fundamental step in the drug design pipeline and a critical question in protein physics. One way to investigate this subject is to computationally predict protein sequences that are compatible with multiple states, i.e., multiple target structures or binding to distinct partners. The goal of engineering such proteins has been termed multispecific protein design. We develop a novel computational framework to efficiently and accurately perform multispecific protein design. This framework utilizes recent advances in probabilistic graphical modeling to predict sequences with low energies in multiple target states. Furthermore, it is also geared to specifically yield positional amino acid probability profiles compatible with these target states. Such profiles can be used as input to randomly bias high‐throughput experimental sequence screening techniques, such as phage display, thus providing an alternative avenue for elucidating the multispecificity of natural proteins and the synthesis of novel proteins with specific functionalities. We prove the utility of such multispecific design techniques in better recovering amino acid sequence diversities similar to those resulting from millions of years of evolution. We then compare the approaches of prediction of low energy ensembles and of amino acid profiles and demonstrate their complementarity in providing more robust predictions for protein design. Proteins 2010. © 2009 Wiley‐Liss, Inc. 相似文献
57.
Ami Bachar Ashraf Al-Ashhab M. Ines M. Soares Menachem Y. Sklarz Roey Angel Eugene D. Ungar Osnat Gillor 《Microbial ecology》2010,60(2):453-461
The exploration of spatial patterns of abundance and diversity patterns along precipitation gradients has focused for centuries
on plants and animals; microbial profiles along such gradients are largely unknown. We studied the effects of soil pH, nutrient
concentration, salinity, and water content on bacterial abundance and diversity in soils collected from Mediterranean, semi-arid,
and arid sites receiving approximately 400, 300, and 100 mm annual precipitation, respectively. Bacterial diversity was evaluated
by terminal restriction fragment length polymorphism and clone library analyses and the patterns obtained varied with the
climatic regions. Over 75% of the sequenced clones were unique to their environment, while ∼2% were shared by all sites, yet,
the Mediterranean and semi-arid sites had more common clones (∼9%) than either had with the arid site (4.7% and 6%, respectively).
The microbial abundance, estimated by phospholipid fatty acids and real-time quantitative PCR assays, was significantly lower
in the arid region. Our results indicate that although soil bacterial abundance decreases with precipitation, bacterial diversity
is independent of precipitation gradient. Furthermore, community composition was found to be unique to each ecosystem. 相似文献
58.
Diamant A Goren M Yokeş MB Galil BS Klopman Y Huchon D Szitenberg A Karhan SU 《Diseases of aquatic organisms》2010,91(2):137-150
A new microsporidian infecting the Mediterranean common stingray Dasyatis pastinaca (Linnaeus, 1758) is described from Iskenderun Bay, Turkey. The parasite invades the disc muscles, producing slender, spindle-shaped subcutaneous swellings that develop into massive, elongated, tumor-like protuberances measuring up to 11 x 4 cm. Severity of the infection may vary from light (1 or 2 small lesions) to intense, with large parts of the dorsal surface covered with lumps and protrusions. These masses contained a yellowish-white caseous substance consisting of degraded host tissue and microsporidian sporophorous vesicles, which in turn contained developing sporonts, sporoblasts and spores. The ripe spore contained a uni-nucleate sporoplasm and large posterior vacuole, and measured 3.8-4.3 x 2.6-2.8 microm. Infection prevalence was 21% in a sample of 143 host individuals examined. All the infected stingray individuals were within the weight class of 300 to 800 g (200 to 305 mm disc width). Phylogenetic analyses of rDNA sequences indicate that this microsporidian belongs to the Pleistophoridae and clusters with species of the genera Ovipleistophora Pekkarinen, Lom & Nilsen, 2002 and Heterosporis Schubert, 1969. However, the morphology, development and host differ distinctly from all reported species, including those belonging to these 2 genera, and it is thus assigned to a newly erected genus and named Dasyatispora levantinae gen. et sp. nov. This is the first record of a microsporidian infection in a batoid. It is also the first microsporidian species to be formally described from an elasmobranch. 相似文献
59.
Shepherd R Singer Michal Amit-Kohn Samuel Weiss Jonathan Rosenblum Guy Maoz Noah Samuels Esther Lukasiewicz Laurence Freedman Ora Paltiel Menachem Itzchaki Meir Niska Menachem Oberbaum 《BMC clinical pharmacology》2010,10(1):1-8
Background
In spite of recent advances in post-operative pain relief, pain following orthopedic surgery remains an ongoing challenge for clinicians. We examined whether a well known and frequently prescribed homeopathic preparation could mitigate post-operative pain.Method
We performed a randomized, double blind, placebo-controlled trial to evaluate the efficacy of the homeopathic preparation Traumeel S® in minimizing post-operative pain and analgesic consumption following surgical correction of hallux valgus. Eighty consecutive patients were randomized to receive either Traumeel tablets or an indistinguishable placebo, and took primary and rescue oral analgesics as needed. Maximum numerical pain scores at rest and consumption of oral analgesics were recorded on day of surgery and for 13 days following surgery.Results
Traumeel was not found superior to placebo in minimizing pain or analgesic consumption over the 14 days of the trial, however a transient reduction in the daily maximum post-operative pain score favoring the Traumeel arm was observed on the day of surgery, a finding supported by a treatment-time interaction test (p = 0.04).Conclusions
Traumeel was not superior to placebo in minimizing pain or analgesic consumption over the 14 days of the trial. A transient reduction in the daily maximum post-operative pain score on the day of surgery is of questionable clinical importance.Trial Registration
This study was registered at ClinicalTrials.gov. # NCT00279513 相似文献60.
Menachem J. Gunzburg Nigus D. Ambaye Jack T. Hertzog Mark P. Del Borgo Stephanie C. Pero David N. Krag Matthew C. J. Wilce Marie-Isabel Aguilar Patrick Perlmutter Jacqueline A. Wilce 《International journal of peptide research and therapeutics》2010,16(3):177-184
Surface plasmon resonance (SPR) is a useful biosensor technique for the study of biomolecular interactions, with the potential
for high-throughput screening of ligand interactions with drug targets. The key to its successful use, however, is in the
appropriate design of the experiment, including the mode of immobilization to the biosensor chip. We report an investigation
of the use of SPR for measuring the affinity of the G7-18NATE peptide ligand for its Grb7-SH2 domain target involved in the
migratory and proliferative potential of cancer cells. Previous studies have shown that the cyclic non-phosphorylated peptide,
G7-18NATE, inhibits Grb7 interactions with upstream binding partners and is able to inhibit both cell migration and proliferation
of cancer cells. We report the synthesis of a biotinylated G7-18NATE covalently attached to a linker (G7-18NATE-ASASASK-Biotin)
and compare its interaction with the Grb7-SH2 domain by SPR using three different immobilization strategies; immobilisation
of the peptide via streptavidin, immobilization of glutathione S-transferase (GST)-Grb7-SH2 domain via anti-GST antibody,
and immobilization of biotinylated Grb7-SH2 domain via streptavidin. This revealed that sensorgrams free from non-specific
binding and displaying simple kinetics were most readily achieved by immobilising the protein rather than the peptide, in
spite of the lower response associated with this method. K
D values of ~300 μM were determined for both strategies at pH 7.4. This compared with a K
D value of 4.4 μM at pH 6 demonstrating the importance of pH on this interaction. Overall, the immobilised protein systems
are most suitable for future comparative screening efforts using SPR. 相似文献