全文获取类型
收费全文 | 240篇 |
免费 | 22篇 |
出版年
2024年 | 1篇 |
2022年 | 1篇 |
2021年 | 7篇 |
2019年 | 2篇 |
2018年 | 6篇 |
2017年 | 2篇 |
2016年 | 4篇 |
2015年 | 10篇 |
2014年 | 6篇 |
2013年 | 9篇 |
2012年 | 15篇 |
2011年 | 13篇 |
2010年 | 16篇 |
2009年 | 7篇 |
2008年 | 14篇 |
2007年 | 13篇 |
2006年 | 11篇 |
2005年 | 6篇 |
2004年 | 11篇 |
2003年 | 14篇 |
2002年 | 6篇 |
2001年 | 8篇 |
2000年 | 4篇 |
1999年 | 3篇 |
1998年 | 3篇 |
1997年 | 4篇 |
1996年 | 1篇 |
1995年 | 3篇 |
1994年 | 3篇 |
1993年 | 3篇 |
1992年 | 5篇 |
1991年 | 2篇 |
1990年 | 4篇 |
1989年 | 6篇 |
1988年 | 5篇 |
1987年 | 5篇 |
1986年 | 4篇 |
1985年 | 4篇 |
1984年 | 3篇 |
1983年 | 1篇 |
1982年 | 3篇 |
1981年 | 2篇 |
1979年 | 3篇 |
1978年 | 3篇 |
1977年 | 1篇 |
1976年 | 2篇 |
1975年 | 1篇 |
1974年 | 1篇 |
1970年 | 1篇 |
排序方式: 共有262条查询结果,搜索用时 281 毫秒
81.
M L Curtin A S Florjancic H R Heyman M R Michaelides R B Garland J H Holms D H Steinman J F Dellaria J Gong C K Wada Y Guo I B Elmore P Tapang D H Albert T J Magoc P A Marcotte J J Bouska C L Goodfellow J L Bauch K C Marsh D W Morgan S K Davidsen 《Bioorganic & medicinal chemistry letters》2001,11(12):1557-1560
Modification of the biphenyl portion of MMP inhibitor 2a gave analogue 2i which is greater than 1000-fold selective against MMP-2 versus MMP-1. The stereospecific synthesis of both enantiomers of 2i was achieved beginning with (S)- or (R)-benzyl glycidyl ether. The (S)-enantiomer, 11 (ABT-770), is orally bioavailable and efficacious in an in vivo model of tumor growth. 相似文献
82.
83.
Mycobacterium smegmatis is a fast-growing model mycobacterial system that shares many features with the pathogenic Mycobacterium tuberculosis while allowing practical proteomics analysis. With the use of shotgun-style mass spectrometry, we provide a large-scale analysis of the M. smegmatis proteomic response to the anti-tuberculosis (TB) drugs isoniazid, ethambutol, and 5-chloropyrazinamide and elucidate the drugs' systematic effects on mycobacterial proteins. A total of 2550 proteins were identified with approximately 5% false-positive identification rate across 60 experiments, representing approximately 40% of the M. smegmatis proteome ( approximately 6500 proteins). Protein differential expression levels were estimated from the shotgun proteomics data, and 485 proteins showing altered expression levels in response to drugs were identified at a 99% confidence level. Proteomic comparison of anti-TB drug responses shows that translation, cell cycle control, and energy production are down-regulated in all three drug treatments. In contrast, systems related to the drugs' targets, such as lipid, amino acid, and nucleotide metabolism, show specific protein expression changes associated with a particular drug treatment. We identify proteins involved in target pathways for the three drugs and infer putative targets for 5-chloropyrazinamide. 相似文献
84.
Spidroin N-terminal domain promotes a pH-dependent association of silk proteins during self-assembly
Spider silks are spun from concentrated solutions of spidroin proteins. The appropriate timing of spidroin assembly into organized fibers must be highly regulated to avoid premature fiber formation. Chemical and physical signals presented to the silk proteins as they pass from the ampulle and through the tapered duct include changes in ionic environment and pH as well as the introduction of shear forces. Here, we show that the N-terminal domain of spidroins from the major ampullate gland (MaSp-NTDs) for both Nephila and Latrodectus spiders associate noncovalently as homodimers. The MaSp-NTDs are highly pH-responsive and undergo a structural transition in the physiological pH range of the spider duct. Tryptophan fluorescence of the MaSp-NTDs reveals a change in conformation when pH is decreased, and the pH at which the transition occurs is determined by the amount and type of salt present. Size exclusion chromatography and pulldown assays both indicate that the lower pH conformation is associated with a significantly increased MaSp-NTD homodimer stability. By transducing the duct pH signal into specific protein-protein interactions, this conserved spidroin domain likely contributes significantly to the silk-spinning process. Based on these results, we propose a model of spider silk assembly dynamics as mediated through the MaSp-NTD. 相似文献
85.
A simple, fast and sensitive method was developed to verify the presence of
the sialyl Lewis(x) antigen on an N-linked glycoprotein. High performance
liquid chromatography-electrospray mass spectrometry (HPLC-ESI/MS) was used
to identify which of the five N-linked glycosylation sites of human plasma
alpha1-acid-glycoprotein (orosomucoid, OMD) contain the sialyl Lewis(x)
antigen. OMD was digested with proteolytic enzymes and analyzed by reversed
phase chromatography coupled with on-line ESI/MS. A tandem mass
spectrometry experiment was designed to detect the presence of the sialyl
Lewis(x) antigen based on the observation of an 803 mass to charge ratio (
m/z ) ion produced in the intermediate pressure region of the ESI
interface. The ESI/MS signal at m/z 803 is consistent with an oxonium ion
for a glycan structure containing NeuAc, Gal, GlcNAc, and Fuc. The identity
of the m/z 803 ion was confirmed by ESI/MS/MS analysis of the m/z 803
fragment ion and comparison with a sialyl Lewis(x) standard. The
stereochemistry and linkage positions were assigned using previous NMR
analysis but could be determined with permethylation analysis if necessary.
The analysis of OMD gave a pattern showing signal for the sialyl Lewis(x)
antigen coeluting with each of the five N-linked glycopeptides. The ability
to monitor sialyl Lewis(x) expression at each of the five sites is of
interest in the study of OMD's role in inflammatory diseases.
相似文献
86.
J P Després C Bouchard R Savard A Tremblay M Marcotte G Thériault 《European journal of applied physiology and occupational physiology》1984,53(1):25-30
The effects of training and detraining on adipose tissue lipolysis were studied in 19 healthy subjects (7 women and 12 men) who were submitted to a 20-week aerobic training program. Thereafter, subjects refrained from exercise for a period of 50 days. Suprailiac fat biopsies were performed before training, after training, and at the end of the detraining period. Mean fat cell diameter and epinephrine stimulated lipolysis (ESL) were assessed on collagenase isolated fat cells. Body density through underwater weighing and skinfolds at seven different sites were also obtained. Training significantly increased ESL (P less than 0.05) in men but not in women. However, ESL values in men returned to pretraining values after the exercise restriction period. No significant changes in women lipolysis were observed under any conditions. Changes in lipolysis were not correlated with changes in body fatness. However, a significant correlation was observed between the increase in ESL produced by training and the subsequent decrease caused by detraining (r = -0.53; P less than 0.05). The present results suggest that lipolysis in fat cells from the female subjects seems to be insensitive to changes in energy expenditure. Moreover, the present study demonstrates that there are high and low responders in adipocytes ESL to variations in habitual energy expenditure. 相似文献
87.
P Mauriège J P Després D Prud'homme M C Pouliot M Marcotte A Tremblay C Bouchard 《Journal of lipid research》1991,32(10):1625-1633
Biopsies of adipose tissue were obtained from two subcutaneous regions (abdominal and femoral) in a sample of 54 men (32 obese and 22 lean subjects). Clonidine-induced antilipolysis in femoral adipose cells was similar in both groups, whereas subcutaneous abdominal adipocytes of obese individuals showed a higher alpha 2-adrenergic response than did subcutaneous abdominal adipose cells from lean subjects. In addition, epinephrine had a biphasic effect in subcutaneous abdominal adipocytes from obese individuals, as it induced antilipolysis at low concentrations, and a net lipolytic response at higher doses. In contrast, the physiological amine promoted lipolysis in subcutaneous abdominal adipose cells of lean subjects. Epinephrine- and clonidine-induced antilipolysis of subcutaneous abdominal adipocytes was positively associated with the level of subcutaneous abdominal fat measured by computed tomography (CT). Finally, men with a high alpha 2-adrenergic response of subcutaneous abdominal fat cells were fatter than those with a low alpha 2-adrenergic component. These results suggest that, in men with a wide range of body fatness, variations in the lipolytic response of subcutaneous abdominal adipose cells to epinephrine appear to involve changes in the functional balance between alpha 2- and beta-adrenoceptors. 相似文献
88.
B S Bochner D W MacGlashan G V Marcotte R P Schleimer 《Journal of immunology (Baltimore, Md. : 1950)》1989,142(9):3180-3186
Mechanisms favoring the recruitment of circulating human basophils to extravascular sites of allergic inflammation are unknown. The basophil secretagogues anti-IgE, and pollen allergens rye grass I and ragweed Ag E (Lol p I and Amb a I) were tested for their ability to promote basophil adherence to umbilical vein endothelial cells. Co-incubation of endothelial cells and basophils with anti-IgE resulted in time and dose-dependent increases in basophil adhesion. These effects were due to activation of the basophil, required both magnesium and calcium, occurred before or in the absence of histamine release, and were seen at concentrations of stimulus below the usual range of secretagogue activity. In contrast, anti-IgE or Ag stimulation of neutrophils, or basophils from donors non-responsive to anti-IgE or Ag with respect to histamine release, had no effect on cell adherence. mAb 60.3, recognizing the CD18 leukocyte adhesion molecule, inhibited anti-IgE-induced enhancement of basophil-endothelial cell binding. Exposure of basophils to low concentrations of Ag in vivo may selectively initiate basophil infiltration into tissue sites of allergic inflammation by enhancing their adherence to endothelium. 相似文献
89.
Synemin and vimentin are components of intermediate filaments in avian erythrocytes 总被引:32,自引:21,他引:11
下载免费PDF全文
![点击此处可从《The Journal of cell biology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Synemin, a high-molecular-weight protein associated with intermediate filaments in muscle, and vimentin, an intermediate-filament subunit found in many different cell types, have been identified by immunologic and electrophoretic criteria as components of intermediate filaments in mature avian erythrocytes. Desmin, the predominant subunit of intermediate filaments in muscle, has not been detected in these cells. Two dimensional immunoautoradiography of proteolytic fragments of synemin and vimentin demonstates that the erythrocyte proteins are highly homologous, if not identical, to their muscle counterparts. Double immunoflurorescence reaveals that erythrocyte synemin and vimentin co-localize in a cytoplasmic network of sinuous filaments that extends from the nucleus to the plasma membrane and resists aggregation by colcemid. Erythrocytes that are attached to glass cover slips can be sonicated to remove nuclei and nonadherent regions of the plasma membrane; this leaves elliptical patches of adherent membrane that retain mats of vimentin- and synemin-containing intermediate filaments, as seen by immunofluorescence and rotary shadowing. Similarly, mechanical enucleation of erythrocyte ghosts in suspension allows isolation of plasma membranes that retain a significant fraction of the synemin and vimentin, as assayed by electrophoresis, and intermediate filaments, as seen in thin sections. Both synemin and vimentin remain insoluble along with spectrin and actin, in solutions containing nonionic detergent and high salt. However, brief exposure of isolated membrane to distilled water releases the synemin and vimentin together in nearly pure form, before the release of significant amounts of spectrin and actin. These data suggest that avian erythrocyte intermeditate filaments are somehow anchored to the plasma membrane; erythrocytes may thus provide a simple system for the study of intermediate filaments and their mode of interaction with membranes. In addition, these data, in conjunction with previous data from muscle, indicate that synemin is capable of associating with either desmin or vimentin and may thus perform a special role in the structure or function of intermediate filaments in erythrocytes as well as muscle. 相似文献
90.
This paper describes the synthesis of a series of new 10β-substituted 4-estrene-3,17-dione analogs (). These compounds, together with a number of known analogs (), have been evaluated as reversible or irreversible inhibitors of human placental microsomal aromatase. The best reversible inhibitor is the 10β-vinyl compound (). The only compounds causing irreversible inhibition of aromatase are the 10β-propargyl compound () and the 10β-difluoromethyl compound (). 相似文献