全文获取类型
收费全文 | 10268篇 |
免费 | 775篇 |
国内免费 | 937篇 |
专业分类
11980篇 |
出版年
2024年 | 14篇 |
2023年 | 139篇 |
2022年 | 355篇 |
2021年 | 538篇 |
2020年 | 361篇 |
2019年 | 448篇 |
2018年 | 418篇 |
2017年 | 319篇 |
2016年 | 473篇 |
2015年 | 633篇 |
2014年 | 784篇 |
2013年 | 830篇 |
2012年 | 952篇 |
2011年 | 939篇 |
2010年 | 549篇 |
2009年 | 496篇 |
2008年 | 541篇 |
2007年 | 520篇 |
2006年 | 444篇 |
2005年 | 351篇 |
2004年 | 267篇 |
2003年 | 292篇 |
2002年 | 209篇 |
2001年 | 165篇 |
2000年 | 148篇 |
1999年 | 154篇 |
1998年 | 91篇 |
1997年 | 74篇 |
1996年 | 92篇 |
1995年 | 67篇 |
1994年 | 45篇 |
1993年 | 34篇 |
1992年 | 54篇 |
1991年 | 40篇 |
1990年 | 27篇 |
1989年 | 33篇 |
1988年 | 13篇 |
1987年 | 19篇 |
1986年 | 13篇 |
1985年 | 14篇 |
1984年 | 9篇 |
1983年 | 11篇 |
1982年 | 3篇 |
1981年 | 1篇 |
1980年 | 1篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
991.
992.
He Pei Wu Long-Fei Bing Peng-Fei Xia Wei Wang Lan Xie Fang-Fei Lu Xin Lei Shu-Feng Deng Fei-Yan 《Molecular and cellular biochemistry》2019,450(1-2):135-147
Molecular and Cellular Biochemistry - The immune responses, involved in recognition of cancer-specific antigens, are of particular interest as this may provide major leads towards developing new... 相似文献
993.
Mammalian Notch1 is modified with two unusual forms of O-linked glycosylation found on epidermal growth factor-like modules 总被引:10,自引:0,他引:10
Moloney DJ Shair LH Lu FM Xia J Locke R Matta KL Haltiwanger RS 《The Journal of biological chemistry》2000,275(13):9604-9611
Notch is a large cell-surface receptor known to be an essential player in a wide variety of developmental cascades. Here we show that Notch1 endogenously expressed in Chinese hamster ovary cells is modified with O-linked fucose and O-linked glucose saccharides, two unusual forms of O-linked glycosylation found on epidermal growth factor-like (EGF) modules. Interestingly, both modifications occur as monosaccharide and oligosaccharide species. Through exoglycosidase digestions we determined that the O-linked fucose oligosaccharide is a tetrasaccharide with a structure identical to that found on human clotting factor IX: Sia-alpha2,3-Gal-beta1, 4-GlcNAc-beta1,3-Fuc-alpha1-O-Ser/Thr. The elongated form of O-linked glucose appears to be a trisaccharide. Notch1 is the first membrane-associated protein identified with either O-linked fucose or O-linked glucose modifications. It also represents the second protein discovered with an elongated form of O-linked fucose. The sites of glycosylation, which fall within the multiple EGF modules of Notch, are highly conserved across species and within Notch homologs. Since Notch is known to interact with its ligands through subsets of EGF modules, these results suggest that the O-linked carbohydrate modifications of these modules may influence receptor-ligand interactions. 相似文献
994.
Gong M Xia M Zhang J Gu J Liu X Cheng J 《Applied microbiology and biotechnology》2012,93(3):1097-1108
A novel antitumor protein, designated RE26, with anti-lymphoma activity was purified from a Tris–HCl buffer extract of Rozites emodensis (Berk.) Moser by three successive steps of ion exchange chromatography. SDS-PAGE and gel filtration chromatography revealed
that RE26 is a monomeric protein of 26 kDa, and isoelectrofocusing assay indicated its isoelectric point of 4.3–4.4. RE26
has high stability over a wide pH range (pH 3–11) but is sensitive to temperature and only stable under 40 °C. Partial amino
acid sequences of two RE26 peptide fragments were determined by Edman degradation as GLEEEETLLLLFFPP and GTEQE. The half-maximal
inhibitory concentration (IC50) of RE26 against tested lymphoma cell lines was around 4 μg/ml. In vitro experiments showed that RE26 could specifically
bind to lymphoma cells; activate the caspases, including caspases 3, 8, and 9 in host cells; and induce apoptosis. Experiments
in nude mice indicated local RE26 injection adjacent to tumor site could inhibit lymphoma formation. 相似文献
995.
996.
摘要: 【目的】构建产气荚膜梭菌(Clostridium perfringens, C.perfringens)α 毒素基因的重组干酪乳杆菌口服疫苗,为产气荚膜梭菌毒素中毒的防治提供有效方法。【方法】将构建的重组产气荚膜梭菌α毒素基因细胞表面型载体pPG1及分泌表达载体pPG2电转化乳酸乳杆菌(Lactobacillus casei L.casei),获得阳性重组菌pPG1-α/ L.casei 393 乳酸乳杆菌表面表达系统和pPG2-α/ L.casei393乳酸乳杆菌分泌表达系统。重组菌以1%乳糖为诱导物,在MRS培养基中进行诱导,通过Western-blot和间接免疫荧光方法鉴定,确定目的蛋白的表达。将重组菌口服免疫BALB/c小鼠,收集免疫小鼠粪便及眼冲洗液及外生殖道黏液样本测定小鼠产生抗α毒素的特异性sIgA 抗体水平,采集小鼠血液样本测定血清中抗α毒素的特异性IgG抗体水平。并对免疫小鼠进行α毒素的腹腔攻毒实验及对获得的抗血清进行α毒素中和试验测定。【结果】重组干酪乳杆菌pPG1-α/ L.casei 393及pPG2-/ L.casei 393免疫小鼠能够产生明显的抗α毒素的sIgA 和IgG 抗体水平,其对α毒素中和试验结果为完全保护。腹腔攻毒实验结果为能抵抗3倍最小致死剂量的α毒素攻击。【结论】表达产气荚膜梭菌α毒素免疫保护性抗原的重组乳酸乳杆菌口服免疫动物能够产生良好的局部和系统体液免疫应答和免疫中和效力。 相似文献
997.
Gating properties conferred on BK channels by the beta3b auxiliary subunit in the absence of its NH(2)- and COOH termini 总被引:2,自引:0,他引:2
Both beta1 and beta2 auxiliary subunits of the BK-type K(+) channel family profoundly regulate the apparent Ca(2)+ sensitivity of BK-type Ca(2)+-activated K(+) channels. Each produces a pronounced leftward shift in the voltage of half-activation (V(0.5)) at a given Ca(2)+ concentration, particularly at Ca(2)+ above 1 microM. In contrast, the rapidly inactivating beta3b auxiliary produces a leftward shift in activation at Ca(2)+ below 1 microM. In the companion work (Lingle, C.J., X.-H. Zeng, J.-P. Ding, and X.-M. Xia. 2001. J. Gen. Physiol. 117:583-605, this issue), we have shown that some of the apparent beta3b-mediated shift in activation at low Ca(2)+ arises from rapid unblocking of inactivated channels, unlike the actions of the beta1 and beta2 subunits. Here, we compare effects of the beta3b subunit that arise from inactivation, per se, versus those that may arise from other functional effects of the subunit. In particular, we examine gating properties of the beta3b subunit and compare it to beta3b constructs lacking either the NH(2)- or COOH terminus or both. The results demonstrate that, although the NH(2) terminus appears to be the primary determinant of the beta3b-mediated shift in V(0.5) at low Ca(2)+, removal of the NH(2) terminus reveals two other interesting aspects of the action of the beta3b subunit. First, the conductance-voltage curves for activation of channels containing the beta3b subunit are best described by a double Boltzmann shape, which is proposed to arise from two independent voltage-dependent activation steps. Second, the presence of the beta3b subunit results in channels that exhibit an anomalous instantaneous outward current rectification that is correlated with a voltage dependence in the time-averaged single-channel current. The two effects appear to be unrelated, but indicative of the variety of ways that interactions between beta and alpha subunits can affect BK channel function. The COOH terminus of the beta3b subunit produces no discernible functional effects. 相似文献
998.
DAMBE (data analysis in molecular biology and evolution) is an integrated software package for converting, manipulating, statistically and graphically describing, and analyzing molecular sequence data with a user-friendly Windows 95/98/2000/NT interface. DAMBE is free and can be downloaded from http://web.hku.hk/~xxia/software/software.htm. The current version is 4.0.36. 相似文献
999.
2,4-Dichlorophenoxyacetate (2,4-D)/alpha-ketoglutarate (alpha-KG) dioxygenase has been purified to apparent homogeneity from Burkholderia cepacia strain 2a, which utilizes 2,4-D as sole carbon source. The enzyme required ferrous ions, and was a homodimer composed of subunits having an Mr of approximately 32,000. The reaction catalysed consumed one mol each of 2,4-D, alpha-KG and dioxygen, with the production of one mol each of succinate, 2,4-dichlorophenol and glyoxylate. Maximum activity was exhibited at pH 7.8 and 25 degrees C, and reactivity was enhanced by the presence of ascorbate and cysteine. Mn2+, Zn2+, Cu2+, Fe3+ and Co2+ were inhibitory, and chemical modification of the dioxygenase revealed that thiol groups were essential for activity. The enzyme was active towards other substituted phenoxyacetates, but reacted most rapidly with 2,4-D. The apparent Michaelis constants for 2,4-D and alpha-KG were 109 and 8.9 microM, respectively. The properties of this enzyme are compared with those of the 2,4-D/alpha-KG dioxygenase from Ralstonia eutropha JMP134, which exhibits a differing N-terminal amino-acid sequence, and a different temperature 'optimum', pH optimum, substrate specificity and sensitivity to thiol-binding reagents. 相似文献
1000.
Chang-An Yu Hua Tian Li Zhang Kai-Ping Deng Sudha K. Shenoy Linda Yu Di Xia Hoeon Kim Johann Deisenhofer 《Journal of bioenergetics and biomembranes》1999,31(3):191-200
The mitochondrial cytochrome bc
1 complex is a multifunctional membrane protein complex. Itcatalyzes electron transfer, proton translocation, peptide processing, and superoxide generation.Crystal structure data at 2.9 Å resolution not only establishes the location of the redox centersand inhibitor binding sites, but also suggests a movement of the head domain of the iron–sulfurprotein (ISP) during bc
1 catalysis and inhibition of peptide-processing activity during complexmaturation. The functional importance of the movement of extramembrane (head) domain ofISP in the bc
1 complex is confirmed by analysis of the Rhodobacter sphaeroides bc
1 complexmutants with increased rigidity in the ISP neck and by the determination of rate constants foracid/base-induced intramolecular electron transfer between [2Fe–2S] and heme c
1 in nativeand inhibitor-loaded beef complexes. The peptide-processing activity is activated in bovineheart mitochondrial bc
1 complex by nonionic detergent at concentrations that inactivate electrontransfer activity. This peptide-processing activity is shown to be associated with subunits Iand II by cloning, overexpression and in vitro reconstitution. The superoxide-generation siteof the cytochrome bc
1 complex is located at reduced b
L and Q–. The reaction is membranepotential-, and cytochrome c-dependent. 相似文献