全文获取类型
收费全文 | 825篇 |
免费 | 79篇 |
出版年
2022年 | 11篇 |
2021年 | 34篇 |
2020年 | 10篇 |
2019年 | 9篇 |
2018年 | 8篇 |
2017年 | 9篇 |
2016年 | 22篇 |
2015年 | 40篇 |
2014年 | 44篇 |
2013年 | 61篇 |
2012年 | 89篇 |
2011年 | 78篇 |
2010年 | 48篇 |
2009年 | 38篇 |
2008年 | 59篇 |
2007年 | 44篇 |
2006年 | 50篇 |
2005年 | 42篇 |
2004年 | 34篇 |
2003年 | 35篇 |
2002年 | 30篇 |
2001年 | 8篇 |
2000年 | 7篇 |
1999年 | 2篇 |
1998年 | 6篇 |
1997年 | 5篇 |
1996年 | 5篇 |
1995年 | 2篇 |
1994年 | 2篇 |
1992年 | 2篇 |
1991年 | 6篇 |
1990年 | 2篇 |
1989年 | 8篇 |
1988年 | 4篇 |
1987年 | 6篇 |
1986年 | 7篇 |
1985年 | 6篇 |
1984年 | 3篇 |
1983年 | 1篇 |
1982年 | 5篇 |
1981年 | 4篇 |
1980年 | 2篇 |
1979年 | 1篇 |
1978年 | 1篇 |
1977年 | 1篇 |
1966年 | 2篇 |
1965年 | 2篇 |
1963年 | 2篇 |
1962年 | 3篇 |
1960年 | 1篇 |
排序方式: 共有904条查询结果,搜索用时 578 毫秒
151.
152.
Lior Rosenfeld Jason Shirian Yuval Zur Noam Levaot Julia M. Shifman Niv Papo 《The Journal of biological chemistry》2015,290(43):26180-26193
The molecular interactions between macrophage colony-stimulating factor (M-CSF) and the tyrosine kinase receptor c-FMS play a key role in the immune response, bone metabolism, and the development of some cancers. Because no x-ray structure is available for the human M-CSF·c-FMS complex, the binding epitope for this complex is largely unknown. Our goal was to identify the residues that are essential for binding of the human M-CSF to c-FMS. For this purpose, we used a yeast surface display (YSD) approach. We expressed a combinatorial library of monomeric M-CSF (M-CSFM) single mutants and screened this library to isolate variants with reduced affinity for c-FMS using FACS. Sequencing yielded a number of single M-CSFM variants with mutations both in the direct binding interface and distant from the binding site. In addition, we used computational modeling to map the identified mutations onto the M-CSFM structure and to classify the mutations into three groups as follows: those that significantly decrease protein stability; those that destroy favorable intermolecular interactions; and those that decrease affinity through allosteric effects. To validate the YSD and computational data, M-CSFM and three variants were produced as soluble proteins; their affinity and structure were analyzed; and very good correlations with both YSD data and computational predictions were obtained. By identifying the M-CSFM residues critical for M-CSF·c-FMS interactions, we have laid down the basis for a deeper understanding of the M-CSF·c-FMS signaling mechanism and for the development of target-specific therapeutic agents with the ability to sterically occlude the M-CSF·c-FMS binding interface. 相似文献
153.
The ability of Najas marina L. to thrive in the presence of the submerged hydrophytes (Myriophyllum spicatum L. and Potamogeton lucens L.) and of an emerged hygrophyte (Scirpus litoralis Schard.) was investigated in Tel Aviv, Israel. Najas plants were unaffected by the presence of Potamogeton lucens and Scirpus litoralis, but were significantly suppressed by Myriophyllum. Bilateral negative relationships exist between Najas and Myriophyllum and these seem to be of an allelophatic nature, depending more on the nature of the accompanying species rather than on their mass. 相似文献
154.
James B. Orenberg Stephen Chan John Calderon Noam Lahav 《Origins of life and evolution of the biosphere》1985,15(2):121-129
The adsorption of 5-AMP onto solid CaSO4 · 2H2O was studied in a saturated suspension as a function of pH and electrolyte concentration. The adsorption is pH-dependent and is directly correlated with the charge on the 5-AMP molecule which is determined by the state of protonation of the N-1 nitrogen of the purine ring and the phosphate oxygens. It is proposed that the binding that occurs between the nucleotide and the salt is electrostatic in nature. The adsorption decreases with increasing ionic strength of the solution which means that in a fluctuating environment of wetting and drying cycles, a biomolecule similar to 5-AMP could be expected to desorb during the drying phase. The results indicate that CaSO4 · 2H2O can serve as a concentrating surface for biomolecules. The significance of this is discussed with regard to the possible role of soluble minerals and their surfaces in a geochemical model consistent with the evolution of the Earth and the origin of life. 相似文献
155.
Shlomo Dagan Alain Beretz Dr. Mati Fridkin Yoav Burstein Zvi Spirer 《Molecular and cellular biochemistry》1985,66(1):5-11
Summary Immunoglobulin G was separated on cellulose phosphate column to afford four distinct protein fractions (CP-I, II, III and IV). 125I-labeled fractions CP-III and CP-IV were found to be capable of binding specifically to normal human erythrocytes. The effect of the four fractions on osmotic resistance of red blood cells (RBC) was studied. RBC were obtained from eight patients with hereditary spherocytosis (HS), from a single parent of two non-related patients, and from five normal donors. RBC fragility of normal and one parent were unaffected by any of the immunoglobulin fractions. In contrast, a small but significant decrease in osmotic resistance was observed when RBC from HS patients and the second parent were incubated with protein fractions CP-III and CP-IV. 相似文献
156.
Dual‐specificity tyrosine phosphorylation‐regulated kinase 2 regulates osteoclast fusion in a cell heterotypic manner
下载免费PDF全文
![点击此处可从《Journal of cellular physiology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Gali Guterman‐Ram Milena Pesic Ayelet Orenbuch Tal Czeiger Anastasia Aflalo Noam Levaot 《Journal of cellular physiology》2018,233(1):617-629
Monocyte fusion into osteoclasts, bone resorbing cells, plays a key role in bone remodeling and homeostasis; therefore, aberrant cell fusion may be involved in a variety of debilitating bone diseases. Research in the last decade has led to the discovery of genes that regulate osteoclast fusion, but the basic molecular and cellular regulatory mechanisms underlying the fusion process are not completely understood. Here, we reveal a role for Dyrk2 in osteoclast fusion. We demonstrate that Dyrk2 down regulation promotes osteoclast fusion, whereas its overexpression inhibits fusion. Moreover, Dyrk2 also promotes the fusion of foreign‐body giant cells, indicating that Dyrk2 plays a more general role in cell fusion. In an earlier study, we showed that fusion is a cell heterotypic process initiated by fusion‐founder cells that fuse to fusion‐follower cells, the latter of which are unable to initiate fusion. Here, we show that Dyrk2 limits the expansion of multinucleated founder cells through the suppression of the fusion competency of follower cells. 相似文献
157.
Miriam Altstein Ezra Dunkelblum Tal Gabay Orna Ben Aziz Irit Schafler Yoav Gazit 《Archives of insect biochemistry and physiology》1995,30(4):307-319
A structure-activity relationship study of Hez-PBAN was performed with respect to its pheromonotropic activity, using Heliothis peltigera as the test animal. The activity of N- and C-terminally derived sequences was examined in a time- and dose-dependent mode. Using a variety of Hez-PBAN-derived fragments at two doses (1 and 10 pmol) and at different times post-injection (5–120 min), we were able to demonstrate that peptides lacking 12 and 16 amino acids from their N-terminus are as potent as the full length PBAN, and that the C-terminally derived hexapeptide was capable of stimulating sex pheromone production to a similar extent as PBAN 1–33NH2, when its activity was analyzed at shorter post-injection times. Within the C-terminal sequence, the amide was found to play a crucial role. In addition, it was observed that the region between amino acids 9 and 13 is important for the biological activity of the full length PBAN. The fact that the pheromonotropic activity of the hexapeptide was similar to that of the full length PBAN, under specific conditions, suggests that this sequence constitutes the biologically active site of the neuropeptide. The discovery that PBAN-derived peptides reacted in a time- and dose-dependent mode, strengthens the assumption that proteolytic enzymes interfere with the pheromonotropic activity of the PBAN-derived fragments. The ability of a variety of peptides to stimulate sex pheromone biosynthesis suggests two possible mechanisms: (1) Existence of multiple pheromonotropic mechanisms which may be mediated by multiple PBAN receptors that are activated at different kinetics; (2) Existence of only one mechanism mediated by short C-terminally derived peptides. In the first case, the C-terminally derived sequences fulfill the conformational requirement of only one class of receptors, and other regions in the PBAN molecule (e.g., 9–13) fulfill the conformational requirements of a second (or other) class of receptors. In the second case, the C-terminally derived sequence is the only conformationally important sequence, and other sequences, which were found to be essential for the biological activity, serve other non-conformational purposes (e.g., protection against proteolytic degradation). © 1995 Wiley-Liss, Inc. 相似文献
158.
159.
Phosphoenolpyruvate carboxylase (PEP carboxylase EC 4.1.1.31) was extracted from various halophytic, semi-halophytic and glycophytic plant species. When the enzyme of those extracts was substrate protected, and in the presence of 1.6 m M PEP in the reaction mixture, the activity of PEP carboxylase was increased by 100 m M NaCl, and the activity range in the presence of NaCl was expanded. No correlation could be established between the response of the enzyme to ions and various plant characteristics, such as taxonomic status, salt tolerance or carbon fixation pathways. Salt activation of PEP carboxylase was substrate (PEP) dependent, but the minimal substrate concentration varied in different species.
Effects of the stabilizing solutes PEP, betaine, proline and glycerol on the kinetic properties of PEP carboxylase from Zea mays (L.) cv. Hazera were analyzed. In the absence of NaCl the slope of the Hill plot (nIt ) tended to rise in the presence of these solutes. Stabilization of the enzyme with betaine or glycerol caused a decrease in K'. while K' and VTO increased in the presence of PEP. NaCl (100 mM) caused an increase in both K' and Vmax in the protected as well as in the unprotected enzyme, except for PEP protection, where K' decreased somewhat. In the presence of the protectants, glycerol and PEP, the effect of NaCl on Vmax , was 2–4 times higher than its effect on the non-protected enzyme. 相似文献
Effects of the stabilizing solutes PEP, betaine, proline and glycerol on the kinetic properties of PEP carboxylase from Zea mays (L.) cv. Hazera were analyzed. In the absence of NaCl the slope of the Hill plot (n
160.
Synaptic function crucially depends on uninterrupted synthesis and degradation of synaptic proteins. While much has been learned on synaptic protein synthesis, little is known on the routes by which synaptic proteins are degraded. Here we systematically studied how inhibition of the ubiquitin‐proteasome system (UPS) affects the degradation rates of thousands of neuronal and synaptic proteins. We identified a group of proteins, including several proteins related to glutamate receptor trafficking, whose degradation rates were significantly slowed by UPS inhibition. Unexpectedly, however, degradation rates of most synaptic proteins were not significantly affected. Interestingly, many of the differential effects of UPS inhibition were readily explained by a quantitative framework that considered known metabolic turnover rates for the same proteins. In contrast to the limited effects on protein degradation, UPS inhibition profoundly and preferentially suppressed the synthesis of a large number of synaptic proteins. Our findings point to the importance of the UPS in the degradation of certain synaptic proteins, yet indicate that under basal conditions most synaptic proteins might be degraded through alternative pathways. 相似文献