全文获取类型
收费全文 | 630篇 |
免费 | 33篇 |
国内免费 | 1篇 |
出版年
2023年 | 2篇 |
2022年 | 5篇 |
2021年 | 11篇 |
2020年 | 5篇 |
2019年 | 11篇 |
2018年 | 10篇 |
2017年 | 13篇 |
2016年 | 13篇 |
2015年 | 36篇 |
2014年 | 26篇 |
2013年 | 34篇 |
2012年 | 63篇 |
2011年 | 56篇 |
2010年 | 29篇 |
2009年 | 24篇 |
2008年 | 48篇 |
2007年 | 37篇 |
2006年 | 35篇 |
2005年 | 48篇 |
2004年 | 23篇 |
2003年 | 45篇 |
2002年 | 28篇 |
2001年 | 10篇 |
2000年 | 5篇 |
1999年 | 8篇 |
1998年 | 3篇 |
1997年 | 4篇 |
1996年 | 3篇 |
1995年 | 1篇 |
1994年 | 1篇 |
1993年 | 1篇 |
1992年 | 1篇 |
1991年 | 1篇 |
1990年 | 1篇 |
1988年 | 2篇 |
1986年 | 1篇 |
1985年 | 3篇 |
1984年 | 2篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1981年 | 2篇 |
1980年 | 1篇 |
1979年 | 2篇 |
1977年 | 2篇 |
1971年 | 1篇 |
1969年 | 1篇 |
1967年 | 1篇 |
1966年 | 2篇 |
1965年 | 1篇 |
排序方式: 共有664条查询结果,搜索用时 312 毫秒
61.
62.
Manninen A Verkade P Le Lay S Torkko J Kasper M Füllekrug J Simons K 《Molecular and cellular biology》2005,25(22):10087-10096
Caveolin-1 has been implicated in apical transport of glycosylphosphatidylinositol (GPI)-anchored proteins and influenza virus hemagglutinin (HA). Here we have studied the role of caveolin-1 in apical membrane transport by generating caveolin-1-deficient Madin-Darby canine kidney (MDCK) cells using retrovirus-mediated RNA interference. The caveolin-1 knockdown (cav1-KD) MDCK cells were devoid of caveolae. In addition, caveolin-2 was retained in the Golgi apparatus in cav1-KD MDCK cells. However, we found no significant alterations in the apical transport kinetics of GPI-anchored proteins or HA upon depletion of caveolin-1. Similar results were obtained using embryonic fibroblasts from caveolin-1-knockout mice. Thus, we conclude that caveolin-1 does not play a major role in lipid raft-mediated biosynthetic membrane trafficking. 相似文献
63.
In 1985, Paterson and Bettger found hypoplastic hematopoiesis in severely zinc-deficient rats. Therefore, we investigated
plasma erythropoietin concentration in zinc-deficient rats. Forty 4-wk-old male Sprague-Dawley rats were assigned into 4 dietary
treatment groups of 10 for the 4-wk study: zinc-deficient group (4.5 mg zinc and 35 mg iron/kg; −Zn), iron-deficient group
(30 mg zinc/kg, no supplemental iron; −Fe), zinc/iron-deficient group (4.5 mg zinc/kg, no supplemental iron; −Zn−Fe), and
control group (AIN-93G; Cont). Water intake determined at d 19 was similar among all treatment groups. At d 27–28, bioimpedance
was measured. The intracellular water/extracellular water ratio was significantly increased in the −Zn group (p<0.05). Compared to the Cont, group, the plasma erythropoietin concentration was increased by iron deficiency and decreased
by zinc deficiency (p<0.01). Hematocrit was significantly decreased in both the −Fe and −Zn−Fe groups and was significantly increased in the −Zn
group (p<0.01). Transferrin saturation in the −Fe and −Zn−Fe groups was significantly lower than the Cont group (p<0.01), and that of the −Zn group was highest among all groups. The low plasma erythropoietin concentration might account
for depressed hematopoiesis associated with zinc deficiency. 相似文献
64.
Chlorella, when heterotrophically cultivated in the dark, is able to grow with Zn2+ at 10-40 mM, which is 10 times the concentration lethal to autotrophically grown cells. However, the lag phase is prolonged with increasing concentrations of Zn2+; for example, in this study, 1 d of the control lag phase was prolonged to about 16 d with Zn2+ at 16.7 mM (x2,000 of the control). Once the cells started to grow, the log phase was finished within 4-6 d regardless of Zn concentration, which was almost the same as that of the control. The photosysystem I reaction center chlorophyll, P700, and the far-red fluorescence were detected only after the late log phase of the growth curve, suggesting that chlorophyll-protein complexes can be organized after cell division has ceased. Interestingly, at more than 16.7 mM of Zn2+, Zn-chlorophyll a was accumulated and finally accounted for about 25% of the total chlorophyll a in the late stationary phase. We found that the Zn-chlorophyll a was present in the thylakoid membranes and not in the soluble fractions of the cells. The rather low fluorescence yield at around 680 nm in the stationary phase suggests that Zn-chlorophyll a can transfer its excitation energy to other chlorophylls. Before accumulation of Zn-chlorophyll a, a marked amount of pheophytin a was temporally accumulated, suggesting that Zn-chlorophyll a could be chemically synthesized via pheophytin a. 相似文献
65.
Characterization of salt-tolerant glutaminase from Stenotrophomonas maltophilia NYW-81 and its application in Japanese soy sauce fermentation 总被引:1,自引:0,他引:1
Wakayama M Yamagata T Kamemura A Bootim N Yano S Tachiki T Yoshimune K Moriguchi M 《Journal of industrial microbiology & biotechnology》2005,32(9):383-390
Glutaminase from Stenotrophomonas maltophilia NYW-81 was purified to homogeneity with a final specific activity of 325 U/mg. The molecular mass of the native enzyme was
estimated to be 41 kDa by gel filtration. A subunit molecular mass of 36 kDa was measured with SDS-PAGE, thus indicating that
the native enzyme is a monomer. The N-terminal amino acid sequence of the enzyme was determined to be KEAETQQKLANVVILATGGTIA.
Besides l-glutamine, which was hydrolyzed with the highest specific activity (100%), l-asparagine (74%), d-glutamine (75%), and d-asparagine (67%) were also hydrolyzed. The pH and temperature optima were 9.0 and approximately 60°C, respectively. The enzyme
was most stable at pH 8.0 and was highly stable (relative activities from 60 to 80%) over a wide pH range (5.0–10.0). About
70 and 50% of enzyme activity was retained even after treatment at 60 and 70°C, respectively, for 10 min. The enzyme showed
high activity (86% of the original activity) in the presence of 16% NaCl. These results indicate that this enzyme has a higher
salt tolerance and thermal stability than bacterial glutaminases that have been reported so far. In a model reaction of Japanese
soy sauce fermentation, glutaminase from S. maltophilia exhibited high ability in the production of glutamic acid compared with glutaminases from Aspergillus oryzae, Escherichia coli, Pseudomonas citronellolis, and Micrococcus luteus, indicating that this enzyme is suitable for application in Japanese soy sauce fermentation. 相似文献
66.
Oteki T Nagase S Yokoyama H Ohya H Akatsuka T Tada M Ueda A Hirayama A Koyama A 《Biochemical and biophysical research communications》2005,332(2):326-331
A rat model for human minimal change nephropathy was obtained by the intravenous injection of adriamycin (ADR) at 5 mg/kg. By using an in vivo electron paramagnetic resonance (EPR) spectrometer operating at 700 MHz, the temporal changes in signal intensities of a nitroxide radical, 4-hydroxyl-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL), in the kidneys of rats with ADR nephropathy were investigated. The decay rate of the EPR signal intensity obtained in the kidney is indicative of the renal reducing ability. It was found that the reducing ability in the kidney declined on the 7th day after ADR administration and recovered after the 14th day. Impairment of the reducing ability occurred before the appearance of continuous urinary protein. The in vitro EPR study showed that this impairment of in vivo renal reducing ability is related to impairment of the reducing ability in the mitochondria. 相似文献
67.
68.
Posteraro P Pascucci M Colombi M Barlati S Giannetti A Paradisi M Mustonen A Zambruno G Castiglia D 《Biochemical and biophysical research communications》2005,338(3):1391-1401
Dystrophic epidermolysis bullosa (DEB) is a rare clinically heterogeneous genodermatosis due to genetic defects in type VII collagen gene (COL7A1). Identification of COL7A1 mutations is a challenge since this gene comprises 118 exons and more than 300 mutations scattered over the gene have been reported. Here, we describe for the first time the use of denaturing high performance liquid chromatography (DHPLC) for COL7A1 mutation detection. To validate the method, exon-specific DHPLC conditions were applied to screen DNA samples from patients carrying known COL7A1 mutations. Abnormal DHPLC profiles were obtained for all known mutations. Subsequent DHPLC analysis of 17 DEB families of unknown genotype allowed the identification of 21 distinct mutations, 9 of which were novel. The DHPLC mutation detection rate was significantly higher compared with our mutation scanning rate with conventional techniques (97% vs 86%), indicating DHPLC as the method of choice for COL7A1 molecular characterization in DEB patients. 相似文献
69.
Abe M Murai M Ichimaru N Kenmochi A Yoshida T Kubo A Kimura Y Moroda A Makabe H Nishioka T Miyoshi H 《Biochemistry》2005,44(45):14898-14906
Studies on the inhibitory mechanism of acetogenins, the most potent inhibitors of mitochondrial complex I (NADH-ubiquinone oxidoreductase), are useful for elucidating the structural and functional features of the terminal electron transfer step of this enzyme. Previous studies of the structure-activity relationship revealed that except for the alkyl spacer linking the two toxophores (i.e., the hydroxylated THF and the gamma-lactone rings), none of the multiple functional groups of these inhibitors is essential for potent inhibition. To elucidate the function of the alkyl spacer, two sets of systematically selected analogues were synthesized. First, the length of the spacer was varied widely. Second, the local flexibility of the spacer was specifically reduced by introducing multiple bond(s) into different regions of the spacer. The optimal length of the spacer for inhibition was approximately 13 carbon atoms. The decrease in the strength of the inhibitory effect caused by elongating the spacer from 13 carbons was much more drastic than that caused by shortening. Local flexibility in a specific region of the spacer was not important for the inhibition. These observations indicate that the active conformation of the spacer is not an extended form, and is not necessarily restricted to a certain rigid shape. Moreover, an analogue in which a spacer covering 10 carbon atoms was hardened into a rodlike shape still maintained a potent inhibitory effect. Our results strongly suggest that the spacer portion is free from steric congestion arising from the putative binding site probably because there is no cavity-like binding site for the spacer portion. The manner of acetogenin binding to the enzyme may not be explained by a simple "key and keyhole" analogy. 相似文献
70.
Maruyama T Yamamoto Y Shimizu A Masuda H Sakai N Sakurai R Asada H Yoshimura Y 《Biology of reproduction》2004,70(1):214-221
Reversible protein tyrosine phosphorylation, coordinately controlled by protein tyrosine kinases and phosphatases, is a critical element in signal transduction pathways regulating a wide variety of biological processes, including cell growth, differentiation, and tumorigenesis. We have previously reported that c-Src belonging to the Src family tyrosine kinase (SFK) becomes dephosphorylated at tyrosine 530 (Y530) and thereby activated during progestin-induced differentiation of human endometrial stromal cells (i.e., decidualization). In this study, to elucidate the role of decidual c-Src activation, we examined whether 4-amino-5-(4-methylphenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (PP1) and 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (PP2), both potent and selective SFK inhibitors, affected the ovarian steroid-induced decidualization in vitro. Unexpectedly, PP1 paradoxically increased the kinase activity of decidual c-Src together with dephosphorylation of Y530 in the presence of ovarian steroids. Concomitantly, PP1 enhanced morphological and functional decidualization, as determined by induction of decidualization markers, such as insulin-like growth factor binding protein-1 and prolactin. PP2 also advanced decidualization along with up-regulation of the active form of c-Src whose Y-530 was dephosphorylated. In contrast to PP1 and PP2, herbimycin A, a tyrosine kinase inhibitor with less specificity for SFKs, showed little enhancing effect on the expression of both IGFBP-1 and active c-Src. These results suggest that SFKs, including c-Src, may play a significant role in stromal cell differentiation, providing a clue for a possible therapeutic strategy to modulate endometrial function by targeting signaling pathway(s) involving SFKs. 相似文献