全文获取类型
收费全文 | 308篇 |
免费 | 35篇 |
专业分类
343篇 |
出版年
2020年 | 2篇 |
2017年 | 4篇 |
2016年 | 6篇 |
2015年 | 12篇 |
2014年 | 13篇 |
2013年 | 9篇 |
2012年 | 15篇 |
2011年 | 18篇 |
2010年 | 13篇 |
2009年 | 11篇 |
2008年 | 16篇 |
2007年 | 24篇 |
2006年 | 13篇 |
2005年 | 10篇 |
2004年 | 17篇 |
2003年 | 17篇 |
2002年 | 16篇 |
2001年 | 7篇 |
2000年 | 17篇 |
1999年 | 12篇 |
1998年 | 4篇 |
1997年 | 3篇 |
1992年 | 7篇 |
1991年 | 4篇 |
1990年 | 3篇 |
1989年 | 2篇 |
1988年 | 3篇 |
1987年 | 2篇 |
1986年 | 4篇 |
1984年 | 1篇 |
1983年 | 3篇 |
1982年 | 2篇 |
1981年 | 3篇 |
1980年 | 2篇 |
1979年 | 2篇 |
1977年 | 2篇 |
1976年 | 1篇 |
1975年 | 3篇 |
1974年 | 9篇 |
1973年 | 3篇 |
1972年 | 3篇 |
1971年 | 6篇 |
1970年 | 2篇 |
1969年 | 1篇 |
1967年 | 3篇 |
1966年 | 3篇 |
1965年 | 2篇 |
1963年 | 1篇 |
1951年 | 1篇 |
1947年 | 1篇 |
排序方式: 共有343条查询结果,搜索用时 15 毫秒
1.
2.
Modification of human growth hormone (hGH) with a low equimolar concentration of fluorescein isothiocyanate (FITC) yielded a derivative containing 1 mol of fluorescein/mol of protein. The site of modification was identified as lysine-70. Lysine-70 of hGH is about 3-fold more reactive than a "normal" lysine in a protein, having pseudo-first-order kinetics Kobs = 110 +/- 7 M-1 min-1 at pH 10.5. The pKa of the lysine was estimated to be 10.7, within the normal range of normal epsilon-lysine moieties in proteins. This higher chemical reactivity seems to favor selective labeling of this moiety at low FITC concentrations. To obtain monomodified derivatives, hGH was derivatized with 0.6 equiv of FITC, and the modified derivatives were separated from unreacted hormone by means of HPLC using a Mono Q column. Its biological activity, determined by Nb2 bioassay, decreased to 40%, and its affinity toward lactogen receptors in Nb2 cells and toward somatogen receptors in bovine liver decreased respectively to 30% and 20%. The present study indicates that out of the seven amino groups of human growth hormone, the epsilon-amino group of lysine-70 is excessively reactive toward FITC. Second, this particular amino group contributes to receptor binding and receptor activation. Lysine-70 is located in the loop between the first and second helix and close to the carboxy-terminal end of the first helix. This contribution is most likely the result of the formation of an electrostatic interaction between the hormone and the receptor.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
3.
Shirvan A Kimron M Holdengreber V Ziv I Ben-Shaul Y Melamed S Melamed E Barzilai A Solomon AS 《The Journal of biological chemistry》2002,277(51):49799-49807
Damage to the optic nerve in mammals induces retrograde degeneration and apoptosis of the retinal ganglion cell (RGC) bodies. The mechanisms that mediate the response of the neuronal cells to the axonal injury are still unknown. We have previously shown that semaphorins, axon guidance molecules with repulsive cues, are capable of mediating apoptosis in cultured neuronal cells (Shirvan, A., Ziv, I., Fleminger, G., Shina, R., He, Z., Brudo, I., Melamed, E., and Brazilai, A. (1999) J. Neurochem. 73, 961-971). In this study, we examined the involvement of semaphorins in an in vivo experimental animal model of complete axotomy of the rat optic nerve. We demonstrate that a marked induction of type III semaphorin proteins takes place in ipsilateral retinas at early stages following axotomy, well before any morphological signs of RGC apoptosis can be detected. Time course analysis revealed that a peak of expression occurred after 2-3 days and then declined. A small conserved peptide derived from semaphorin 3A that was previously shown to induce neuronal death in culture was capable of inducing RGC loss upon its intravitreous injection into the rat eye. Moreover, we demonstrate a marked inhibition of RGC loss when axotomized eyes were co-treated by intravitreous injection of function-blocking antibodies against the semaphorin 3A-derived peptide. Marked neuronal protection from degeneration was also observed when the antibodies were applied 24 h post-injury. We therefore suggest that semaphorins are key proteins that modulate the cell fate of axotomized RGC. Neutralization of the semaphorin repulsive function may serve as a promising new approach for treatment of traumatic injury in the adult mammalian central nervous system or of ophthalmologic diseases such as glaucoma and ischemic optic neuropathy that induce apoptotic RGC death. 相似文献
4.
Erik?Sahai Jeffrey?WyckoffEmail author Ulrike?Philippar Jeffrey?E?Segall Frank?Gertler John?Condeelis 《BMC biotechnology》2005,5(1):14
Background
The development of multiphoton laser scanning microscopy has greatly facilitated the imaging of living tissues. However, the use of genetically encoded fluorescent proteins to distinguish different cell types in living animals has not been described at single cell resolution using multiphoton microscopy. 相似文献5.
6.
Nina O. Nielsen Marit E. J?rgensen Henrik Friis Mads Melbye Bolette Soborg Charlotte Jeppesen Marika Lundqvist Arieh Cohen David M. Hougaard Peter Bjerregaard 《PloS one》2014,9(12)
Background
Low vitamin D status may be pronounced in Arctic populations due to limited sun exposure and decreasing intake of traditional food.Objective
To investigate serum 25(OH)D3 as a measure of vitamin D status among adult Inuit in Greenland, predictors of low serum 25(OH)D3 concentrations and the trend from 1987 to 2005–2010.Design
A total of 2877 randomly selected Inuit (≥18 years) from the Inuit Health in Transition study were included. A sub-sample (n = 330) donated a blood sample in 1987 which allowed assessment of time trends in vitamin D status.Results
The geometric mean serum 25(OH)D3 (25[OH]D2 concentrations were negligible and not reported) in 2005–2010 was lowest among the 18–29 year old individuals (30.7 nmol/L; 95% CI: 29.7; 31.7) and increased with age. In all age-groups it decreased from 1987 to 2005–2010 (32%–58%). Low 25(OH)D3 concentrations (<50 nmol/L) were present in 77% of the 18–29 year old and decreased with age. A characteristic seasonal variation in 25(OH)D3 concentrations was observed (range 33.2–57.1 nmol/L, p<0.001), with the highest concentrations in August to October. Age (2.0% per year increase; CI: 1.7, 2.2), female gender (7.1%; CI: 2.0; 12.5), alcohol intake (0.2% per increase in drinks/week; 0.0; 0.4), and traditional diet (10.0% per 100 g/d increase; CI: 7.9; 12.1) were associated with increased serum 25(OH)D3, whereas smoking (−11.6%; CI: −16.2; −6.9), BMI (−0.6%; CI: −1.1; −0.2) and latitude (−0.7% per degree increase; CI: −1.3; −0.2) were associated with decreased concentrations.Conclusion
We identified a remarkable decrease in vitamin D status from 1987 to 2005–2010 and a presently low vitamin D status among Inuit in Greenland. A change away from a traditional diet may well explain the observed decline. The study argues for the need of increased dietary intake of vitamin D and supplementation might be considered. 相似文献7.
Herman A Bignon C Daniel N Grosclaude J Gertler A Djiane J 《The Journal of biological chemistry》2000,275(9):6295-6301
Although homo- or heterodimerization are common mechanisms for activation of cytokine receptors, cross-talk between two distinct receptors in this superfamily has been never shown. Here we show a physiologically relevant example indicating that such an interaction does occurs, thus raising the hypothesis that heterodimerization between distinct cytokine receptors may be a novel mechanism contributing to the diversity of cytokine signaling. These findings were documented using both surface plasmon resonance and gel filtration experiments and show that ovine placental lactogen (PL) heterodimerizes the extracellular domains (ECDs) of ruminant growth hormone receptor (GHR) and prolactin receptor (PRLR). We also show that PL or PL analogues that exhibit little or no activity in cells transfected with PRLRs and no activity in cells transfected with ovine GHRs exhibit largely enhanced activity in cells cotransfected with both PRLRs and GHRs. Furthermore, chimeric receptors consisting of cytosolic and transmembrane part of ovine GHR or ovine PRLR and ECDs of human granulocyte-macrophage colony-stimulating factor receptor (GM-CSFR) alpha or beta were constructed. Upon transfection into Chinese hamster ovary cells along with reporter luciferase gene and stimulation by GM-CSF, a significant increase in luciferase activity occurred when GM-CSFR-alpha-PRLR and GM-CSFR-beta-GHR or GM-CSFR-alpha-GHR and GM-CSRR-beta-PRLR were cotransfected. In conclusion, we show that ovine PL is capable of functional heterodimerization of GHR and PRLR and that when their cytosolic parts, coupled to the ECD of GM-CSF receptors, are heterodimerized by GM-CSF, they are capable of transducing biological signal. 相似文献
8.
The Ena-VASP homology (EVH1) domain is a protein interaction module found in several proteins that are involved in transducing migratory and morphological signals into cytoskeletal reorganization. EVH1 specifically recognizes proline-rich sequences in its binding partners and directs the localization and formation of multicomponent assemblies involved in actin-based motile processes and neural development. The structure of the complex between an EVH1 domain and the target peptide sequence EFPPPPT identifies the interactions responsible for recognition and distinguishes it from other proline-rich binding modules, including SH3 and WW domains. Surprisingly, the EVH1 domain has structural similarity to pleckstrin homology (PH), phosphotyrosine-binding (PTB) and ran-binding (RanBD) domains. 相似文献
9.
10.