全文获取类型
收费全文 | 2585篇 |
免费 | 122篇 |
出版年
2024年 | 2篇 |
2023年 | 14篇 |
2022年 | 42篇 |
2021年 | 66篇 |
2020年 | 37篇 |
2019年 | 71篇 |
2018年 | 71篇 |
2017年 | 45篇 |
2016年 | 102篇 |
2015年 | 138篇 |
2014年 | 149篇 |
2013年 | 196篇 |
2012年 | 261篇 |
2011年 | 240篇 |
2010年 | 154篇 |
2009年 | 126篇 |
2008年 | 188篇 |
2007年 | 170篇 |
2006年 | 115篇 |
2005年 | 106篇 |
2004年 | 92篇 |
2003年 | 79篇 |
2002年 | 55篇 |
2001年 | 38篇 |
2000年 | 34篇 |
1999年 | 27篇 |
1998年 | 10篇 |
1997年 | 10篇 |
1995年 | 4篇 |
1993年 | 8篇 |
1992年 | 12篇 |
1991年 | 4篇 |
1990年 | 1篇 |
1989年 | 5篇 |
1988年 | 5篇 |
1986年 | 5篇 |
1985年 | 2篇 |
1983年 | 1篇 |
1982年 | 3篇 |
1981年 | 1篇 |
1980年 | 1篇 |
1979年 | 1篇 |
1976年 | 2篇 |
1975年 | 2篇 |
1973年 | 1篇 |
1970年 | 1篇 |
1969年 | 3篇 |
1968年 | 1篇 |
1967年 | 3篇 |
1965年 | 1篇 |
排序方式: 共有2707条查询结果,搜索用时 140 毫秒
101.
AMPA glutamate receptors play a crucial role in brain functions such as synaptic plasticity and development. We have studied the chemo-architecture of the AMPA glutamate receptor subtype GluR2/3 in the hamster visual cortex by immunocytochemistry and compared it with the distribution of the calcium-binding proteins, calbindin D28K and calretinin. Anti-GluR2/3-immunoreactive (IR) neurons were predominantly located in layers II/III, V, and VI, and the majority of the labeled neurons were round or oval. However, many pyramidal cells in layer V were also labeled. Two-color immunofluorescence revealed that none of the GluR2/3-IR neurons contained calbindin D28 K or calretinin. Thus specific layers of neurons express the GluR2/3 subunit and these do not correlate with expression of calbindin D28K and calretinin. 相似文献
102.
Lee CK Lee CU Kim JH Son BC Kim DH Lee CH Kim HD Kim JW Yoon YD Kang SG Moon DH 《Molecules and cells》2003,15(1):114-121
This study was performed to investigate the effects of Aroclor 1254 (A1254), a commercial polychlorinated biphenyl mixture, on the expression of rat placental prolactin (PRL) family genes and reproductive activity. Placental lactogen-Iv and -II, and prolactin-like protein-A and -C mRNA levels were significantly decreased in the placentas of A1254-treated rats in a dose-dependent manner. The mRNA levels of Pit-1alpha and beta isotypes, which are involved in the regulation of PRL family gene expression, were also decreased in the A1254-treated rat placenta. In the rat placental junctional zone, high-dose A1254 (25 mg/kg B.W.) treatment reduced the number of spongiotrophoblasts, cells in which the PRL family genes are expressed. Finally, maternal exposure to A1254 was shown to have significant toxic effects on reproductive activity, including embryonic and placental growth retardation, delay of parturition, and reduction of the number of pups per litter. The results of the present study indicated that A1254 has an inhibitory effect on PRL family, Pit-1alpha, and beta gene expression in the rat placenta, leading to significant toxic effects on reproductive activity in rats. 相似文献
103.
A functional interaction between chromogranin B and the inositol 1,4,5-trisphosphate receptor/Ca2+ channel 总被引:2,自引:0,他引:2
Thrower EC Choe CU So SH Jeon SH Ehrlich BE Yoo SH 《The Journal of biological chemistry》2003,278(50):49699-49706
Chromogranins A and B (CGA and CGB) are high capacity, low affinity calcium (Ca2+) storage proteins found in many cell types most often associated with secretory granules of secretory cells but also with the endoplasmic reticulum (ER) lumen of these cells. Both CGA and CGB associate with inositol 1,4,5-trisphosphate receptor (InsP3R) in a pH-dependent manner. At an intraluminal pH of 5.5, as found in secretory vesicles, both CGA and CGB bind to the InsP3R. When the intraluminal pH is 7.5, as found in the ER, CGA totally dissociates from InsP3R, whereas CGB only partially dissociates. To investigate the functional consequences of the interaction between the InsP3R and CGB monomers or CGA/CGB heteromers, purified mouse InsP3R type I were fused to planar lipid bilayers and activated by 2 microM InsP3. In the presence of luminal CGB monomers or CGA/CGB heteromers the InsP3R/Ca2+ channel open probability and mean open time increased significantly. The channel activity remained elevated when the pH was changed to 7.5, a reflection of CGB binding to the InsP3R even at pH 7.5. These results suggest that CGB may play an important modulatory role in the control of Ca2+ release from the ER. Furthermore, the difference in the ability of CGA and CGB to regulate the InsP3R/Ca2+ channel and the variability of CGA/CGB ratios could influence the pattern of InsP3-mediated Ca2+ release. 相似文献
104.
Hoon Kim D Jeon Choi S Kook S Kim W Keun Song W 《Biochemical and biophysical research communications》2003,300(1):141-148
We previously demonstrated caspase-mediated cleavage of p130cas during apoptosis and identified two caspase-3 cleavage sites [1]. In this study, we investigated the phosphorylation-dependent cleavage of p130cas in apoptotic Rat-1 fibroblast cells. Lysophosphatidic acid and fibronectin induced p130cas phosphorylation, which in turn resulted in resistance to caspase-mediated cleavage. Alternatively, dephosphorylation by calf intestinal alkaline phosphatase, PP1, and LAR stimulated cleavage of p130cas by caspase-3, generating a 31-kDa fragment. During apoptosis, p130cas dephosphorylation seems to precede its cleavage. The phosphorylation of tyrosine and serine residues immediately adjacent to the two cleavage sites (DVPD(416) and DSPD(748)) strongly affected p130cas cleavage by caspase-3, both in vitro and in vivo. Furthermore, the generation of the 31-kDa cleavage fragment was strongly regulated by phosphorylation of a tyrosine residue at position 751 (DSPD(748) and GQY(751)). Our results collectively suggest that degradation of p130cas during apoptosis is modulated in a phosphorylation-dependent manner. 相似文献
105.
Discriminant analysis through a semiparametric model 总被引:1,自引:0,他引:1
106.
IL-4 augments anisomycin-induced p38 activation via Akt pathway in a follicular dendritic cell (FDC)-like line 总被引:3,自引:0,他引:3
Prediction of medulloblastoma clinical outcome is crucial to personalizing treatment, both to identify high-risk patients for aggressive or alternative therapy and to spare those at low risk from excessive treatment. The best predictors [Pomeroy et al. (2002) Nature 415, 436-442], based on gene expression monitoring at diagnosis, have shown much less accuracy in recognizing patients with eventual failed outcomes - <50% for the predictor making fewest total errors - than those who would survive, while a single gene predictor exhibited reverse asymmetry. Such inaccuracy in recognizing one of the outcomes is a problem for clinical use. We hypothesized that a non-linear model could be built to significantly improve prediction of medulloblastoma outcome, thereby promoting use of gene-expression-based predictors in a clinical setting. In fact, this approach resulted in fewer errors and much less asymmetry in prediction, and bidirectional accuracy of about 80% could be obtained via its combination with other methods. Indeed, three combinations of methods were identified that yielded significantly better predictions of clinical outcome than previously attained, making feasible predictors of medulloblastoma treatment response with greatly improved bidirectional accuracy essential for clinical use. 相似文献
107.
The gene encoding phosphoglucose isomerase was cloned from Thermococcus litoralis, and functionally expressed in Escherichia coli. The purified enzyme, a homodimer of 21.5 kDa subunits, was biochemically characterized. The inhibition constants for four competitive inhibitors were determined. The enzyme contained 1.25 mol Fe and 0.24 mol Zn per dimer. The activity was enhanced by the addition of Fe(2+), but inhibited by Zn(2+) and EDTA. Enzymes with mutations in conserved histidine and glutamate residues in their cupin motifs contained no metals, and showed large decreases in k(cat). The circular dichroism spectra of the mutant enzymes and the wild type enzyme were essentially the same but with slight differences. 相似文献
108.
Characterization of the Xanthomonas axonopodis pv. glycines Hrp pathogenicity island 总被引:6,自引:0,他引:6
下载免费PDF全文
![点击此处可从《Journal of bacteriology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
We sequenced an approximately 29-kb region from Xanthomonas axonopodis pv. glycines that contained the Hrp type III secretion system, and we characterized the genes in this region by Tn3-gus mutagenesis and gene expression analyses. From the region, hrp (hypersensitive response and pathogenicity) and hrc (hrp and conserved) genes, which encode type III secretion systems, and hpa (hrp-associated) genes were identified. The characteristics of the region, such as the presence of many virulence genes, low G+C content, and bordering tRNA genes, satisfied the criteria for a pathogenicity island (PAI) in a bacterium. The PAI was composed of nine hrp, nine hrc, and eight hpa genes with seven plant-inducible promoter boxes. The hrp and hrc mutants failed to elicit hypersensitive responses in pepper plants but induced hypersensitive responses in all tomato plants tested. The Hrp PAI of X. axonopodis pv. glycines resembled the Hrp PAIs of other Xanthomonas species, and the Hrp PAI core region was highly conserved. However, in contrast to the PAI of Pseudomonas syringae, the regions upstream and downstream from the Hrp PAI core region showed variability in the xanthomonads. In addition, we demonstrate that HpaG, which is located in the Hrp PAI region of X. axonopodis pv. glycines, is a response elicitor. Purified HpaG elicited hypersensitive responses at a concentration of 1.0 micro M in pepper, tobacco, and Arabidopsis thaliana ecotype Cvi-0 by acting as a type III secreted effector protein. However, HpaG failed to elicit hypersensitive responses in tomato, Chinese cabbage, and A. thaliana ecotypes Col-0 and Ler. This is the first report to show that the harpin-like effector protein of Xanthomonas species exhibits elicitor activity. 相似文献
109.
Negative regulation of T cell antigen receptor-mediated Crk-L-C3G signaling and cell adhesion by Cbl-b 总被引:4,自引:0,他引:4
Zhang W Shao Y Fang D Huang J Jeon MS Liu YC 《The Journal of biological chemistry》2003,278(26):23978-23983
It was previously reported that Cbl-b associates with Crk-L in Jurkat T cells. However, the physiological significance of such association remains unclear. Here we examined a regulatory role of Cbl-b in Crk-L-C3G signaling pathway. We found that Cbl-b associates with, and induces, ubiquitin conjugation to Crk-L, which requires a functional RING finger. Cbl-b deficiency does not affect Crk-L stability, but its association with C3G. In Cbl-b-/- T cells, the interaction between Crk-L and C3G, and the activity of the small GTPase Rap1, are increased. Cbl-b-/- T cells also display increased adhesion and cell surface binding to ICAM-1, a finding that is supported by the enhanced clustering of LFA-1 in Cbl-b-/- T cells in response to TCR stimulation. Thus, Cbl-b plays a negative role in Crk-L-C3G-mediated Rap1 and LFA-1 activation in T cells. 相似文献
110.
Suh YG Kim YH Park MH Choi YH Lee HK Moon JY Min KH Shin DY Jung JK Park OH Jeon RO Park HS Kang SA 《Bioorganic & medicinal chemistry letters》2001,11(4):559-562
The structure-activity relationship and molecular modelings of a novel pimarane COX-2 inhibitor are reported. Particularly, a series of linker extended analogues designed on the basis of these studies exhibited significantly enhanced COX-2 inhibitory activities and selectivities. 相似文献