全文获取类型
收费全文 | 1524篇 |
免费 | 79篇 |
出版年
2023年 | 3篇 |
2022年 | 3篇 |
2021年 | 13篇 |
2020年 | 11篇 |
2019年 | 20篇 |
2018年 | 19篇 |
2017年 | 26篇 |
2016年 | 29篇 |
2015年 | 46篇 |
2014年 | 63篇 |
2013年 | 79篇 |
2012年 | 84篇 |
2011年 | 107篇 |
2010年 | 72篇 |
2009年 | 57篇 |
2008年 | 91篇 |
2007年 | 103篇 |
2006年 | 97篇 |
2005年 | 82篇 |
2004年 | 112篇 |
2003年 | 111篇 |
2002年 | 103篇 |
2001年 | 16篇 |
2000年 | 12篇 |
1999年 | 27篇 |
1998年 | 27篇 |
1997年 | 13篇 |
1996年 | 18篇 |
1995年 | 8篇 |
1994年 | 20篇 |
1993年 | 12篇 |
1992年 | 14篇 |
1991年 | 12篇 |
1990年 | 12篇 |
1989年 | 13篇 |
1988年 | 6篇 |
1987年 | 4篇 |
1986年 | 3篇 |
1985年 | 6篇 |
1984年 | 8篇 |
1983年 | 2篇 |
1982年 | 8篇 |
1981年 | 4篇 |
1980年 | 4篇 |
1978年 | 6篇 |
1977年 | 4篇 |
1976年 | 6篇 |
1974年 | 1篇 |
1972年 | 1篇 |
1970年 | 2篇 |
排序方式: 共有1603条查询结果,搜索用时 877 毫秒
101.
Shibata Y Kamata T Kimura M Yamashita M Wang CR Murata K Miyazaki M Taniguchi M Watanabe N Nakayama T 《Journal of immunology (Baltimore, Md. : 1950)》2002,169(4):2134-2140
The central role for Th2 cells in the development of Ag-induced airway hyperresponsiveness and eosinophilic inflammation is well documented. We have reported a crucial role for TCR-induced activation of the Ras/extracellular signal-regulated kinase mitogen-activated protein kinase cascade in Th2 cell differentiation. Here, we show that the development of both OVA-induced airway hyperresponsiveness and eosinophilic airway inflammation in a mouse asthma model are attenuated in transgenic mice by the overexpression of enzymatically inactive Ras molecules in T cells. In addition, reduced levels of IL-5 production and eosinophilic inflammation induced by nematode infection (Nippostrongylus brasiliensis or Heligmosomoides polygyrus) were detected. Thus, the level of Ras activation in T cells appears to determine Th2-dependent eosinophilic inflammation and Ag-induced airway hyperresponsiveness. 相似文献
102.
Maejima H Kinoshita E Yuki T Yakehiro M Seyama I Yamaoka K 《Biochemical and biophysical research communications》2002,295(2):452-457
We located a novel binding site for grayanotoxin on the cytoplasmic linkers of voltage-dependent cardiac (rH1) or skeletal-muscle (mu 1) Na(+) channel isoforms (segments S4-S5 in domains D1 and D4), using the alanine scanning substitution method. GTX-modification of Na(+) channels, transiently expressed in HEK 293 cells, was evaluated under whole-cell voltage clamp, from the ratio of maximum chord conductance for modified and unmodified Na(+) channels. In mu 1, mutations K237A, L243A, S246A, K248A, K249A, L250A, S251A, or T1463A, caused a moderate, but statistically significant decrease in this ratio. On making corresponding mutations in rH1, only L244A dramatically reduced the ratio. Because in mu 1, the serine at position 251 is the only heterologous residue with respect to rH1 (Ala-252), we made a double mutant L243A&S251A to match the sequence of mu 1 and rH1 in S4-S5 linkers of both domains. This double mutation resulted in a significant decrease in the ratio, to the same extent as L244A substitution in rH1 did, indicating that the site at Leu-244 in rH1 or at Leu-243 in mu 1 is a novel one, exhibiting a synergistic effect of grayanotoxin. 相似文献
103.
104.
Chiral synthesis of secondary alcohols of both the (S)- and (R)-enantiomer with extremely high enantioselectivities (up to >99% ee) using a biocatalyst, Geotrichum candidum, is reviewed. Resting cell and dried-cell preparation using acetone were applied to oxidation, reduction, and deracemization reactions. Many methods to improve the reactivity and enantioselectivity of the reactions were developed. For example, additives such as secondary alcohols and hydrophobic resin (Amberlite XAD) were used in nonaqueous reaction media such as organic and supercritical solvents as well as in aqueous ones. As a result, optically pure alcohols of both enantiomers were synthesized on a gram scale. 相似文献
105.
Determination of the stereochemistry of (-)-koninginin A by an X-ray analysis of its synthetic sample 总被引:1,自引:0,他引:1
The absolute configuration of (-)-koninginin A [10-hexyl-11, 12-dioxatricyclo[7.2. 1.0<1 ,6>]dodecane-2,5-diol (1)], the antibiotic metabolite of Trichoderma koningii and T. harzianum, was determined as 1S, 2R, 5S, 6S, 9S, 10S by an X-ray crystallographic analysis of its synthetic sample coupled with the established stereochemical outcome of Sharpless asymmetric dihydroxylation used as the key reaction to prepare intermediate 4. 相似文献
106.
The vertebrate brain is regionalized during development into forebrain, midbrain and hindbrain. Fibroblast growth factor 8 (FGF8) is expressed in the midbrain/hindbrain boundary (MHB) and functions as an organizer molecule. Previous studies demonstrated that the brain of basal chordates or ascidians is also regionalized at least into fore/midbrain and hindbrain. To better understand the ascidian brain regionalization, the expression of the Ciona Fgf8/17/18 gene was compared with the expression of Otx, En and Pax2/5/8 genes. The expression pattern of these genes resembled that of the genes in the vertebrate forebrain, midbrain, MHB and hindbrain, each of those domains being characterized by sole or combined expression of Otx, Pax2/5/8, En and Fgf8/17/18. In addition, the putative forebrain and midbrain expressed Ci-FgfL and Ci-Fgf9/16/20, respectively. Therefore, the regionalization of the ascidian larval central nervous system was also marked by the expression of Fgf genes. 相似文献
107.
Establishment and characterization of a cell-line originated from human mucinous cystadenocarcinoma of the ovary 总被引:2,自引:0,他引:2
We recently established a cell line (designated 371M) derived from an ovarian mucinous cystadenocarcinoma. The tumor cells were obtained from the ascitic fluid of a 54-year-old Japanese woman while she was undergoing surgery. Adjuvant chemotherapy (combined paclitaxel and carboplatin) was administered, but was ineffective, and she died about 4 months after surgery. The 371M cells continuously propagated in vitro over a period of about 50 months and, to date, have undergone over 100 passages. They proliferated in a monolayered sheet with doubling times of 84 h and 37 h in the 10th and 34th passages, respectively. When transplanted into nude mice, the tumor histopathologically resembled the structure of the original tumor. The 371M cells secreted high levels of CA125 and CA19-9 into the culture medium. There were several abnormal chromosomes in all karyotypes selected at random. Sensitivity of 371M cells to a variety of anti-cancer drugs was examined by in vitro MTT assay, and the results suggested that CPT-11 and CDDP were more effective against 371M cells than other anti-cancer agents. 相似文献
108.
MAP kinase cascades in elicitor signal transduction 总被引:3,自引:0,他引:3
Suzuki K 《Journal of plant research》2002,115(3):0237-0244
Protein kinases play important roles in elicitor signal transduction. In this article, I describe the current view of the
role of mitogen-activated protein kinase (MAPK) cascades in elicitor signal transduction of plant cells based on our own research
and recent developments in this field. In the past several years, it has become apparent that MAPK cascades play important
roles in elicitor signal transduction in plants. Our early studies demonstrated the identification of p47 MAPK in tobacco
as an elicitor-responsive protein kinase and possible involvement of p47 MAPK in elicitor signal transduction to induce defense
responses, including defense gene expression and hypersensitive cell death. However, the molecular identity of p47 MAPK is
still unclear. Recent important studies suggest that tobacco MAPK cascades that include SIPK, and/or WIPK, and NtMEK2, an
upstream kinase for both SIPK and WIPK, have a crucial function in induction of defense responses and hypersensitive cell
death. The orthologs of these protein kinases in Arabidopsis and alfalfa are also suggested to have similar functions. Furthermore, the identification of loss-of-function mutation in
Arabidopsis reveals a negative regulatory role for putative MAPK cascades in plant defense mechanisms.
Received: February 7, 2002 / Accepted: February 25, 2002 相似文献
109.
110.
Role of the Rab GTP-binding protein Ypt3 in the fission yeast exocytic pathway and its connection to calcineurin function 下载免费PDF全文
Cheng H Sugiura R Wu W Fujita M Lu Y Sio SO Kawai R Takegawa K Shuntoh H Kuno T 《Molecular biology of the cell》2002,13(8):2963-2976
A genetic screen for mutations synthetically lethal with fission yeast calcineurin deletion led to the identification of Ypt3, a homolog of mammalian Rab11 GTP-binding protein. A mutant with the temperature-sensitive ypt3-i5 allele showed pleiotropic phenotypes such as defects in cytokinesis, cell wall integrity, and vacuole fusion, and these were exacerbated by FK506-treatment, a specific inhibitor of calcineurin. Green fluorescent protein (GFP)-tagged Ypt3 showed cytoplasmic staining that was concentrated at growth sites, and this polarized localization required the actin cytoskeleton. It was also detected as a punctate staining in an actin-independent manner. Electron microscopy revealed that ypt3-i5 mutants accumulated aberrant Golgi-like structures and putative post-Golgi vesicles, which increased remarkably at the restrictive temperature. Consistently, the secretion of GFP fused with the pho1(+) leader peptide (SPL-GFP) was abolished at the restrictive temperature in ypt3-i5 mutants. FK506-treatment accentuated the accumulation of aberrant Golgi-like structures and caused a significant decrease of SPL-GFP secretion at a permissive temperature. These results suggest that Ypt3 is required at multiple steps of the exocytic pathway and its mutation affects diverse cellular processes and that calcineurin is functionally connected to these cellular processes. 相似文献