全文获取类型
收费全文 | 1388篇 |
免费 | 101篇 |
国内免费 | 2篇 |
出版年
2022年 | 11篇 |
2021年 | 24篇 |
2020年 | 13篇 |
2019年 | 17篇 |
2018年 | 22篇 |
2017年 | 17篇 |
2016年 | 25篇 |
2015年 | 36篇 |
2014年 | 42篇 |
2013年 | 88篇 |
2012年 | 82篇 |
2011年 | 62篇 |
2010年 | 59篇 |
2009年 | 48篇 |
2008年 | 67篇 |
2007年 | 66篇 |
2006年 | 59篇 |
2005年 | 57篇 |
2004年 | 47篇 |
2003年 | 29篇 |
2002年 | 46篇 |
2001年 | 40篇 |
2000年 | 33篇 |
1999年 | 27篇 |
1998年 | 13篇 |
1997年 | 12篇 |
1996年 | 17篇 |
1995年 | 10篇 |
1993年 | 13篇 |
1992年 | 20篇 |
1991年 | 24篇 |
1990年 | 19篇 |
1989年 | 32篇 |
1988年 | 21篇 |
1987年 | 20篇 |
1986年 | 16篇 |
1985年 | 30篇 |
1984年 | 22篇 |
1982年 | 12篇 |
1981年 | 14篇 |
1979年 | 14篇 |
1978年 | 9篇 |
1977年 | 13篇 |
1976年 | 14篇 |
1975年 | 9篇 |
1974年 | 14篇 |
1973年 | 9篇 |
1972年 | 10篇 |
1971年 | 9篇 |
1966年 | 11篇 |
排序方式: 共有1491条查询结果,搜索用时 187 毫秒
121.
122.
Complexes of four peptides [KWGK, KGWK, K(6MeW)GK, KG(6MeW)K] with the nucleic acids [poly(A), poly(C), poly(U), poly(I), and rG(8)] have been investigated by phosphorescence and optically detected magnetic resonance (ODMR) spectroscopy. The intrinsic spectroscopic probes used in these studies are tryptophan (W) and 6-methyltryptophan (6MeW). Binding to the nucleic acids results in a red-shift of the phosphorescence 0,0-band (delta E(0,0)) of the aromatic residue as well as a reduction of its zero-field splitting parameter (delta D). Results are compared with earlier studies of the HIV-1 nucleocapsid protein, NCp7, that contains a single tryptophan residue (Trp37) within a retroviral zinc finger sequence. Binding of poly(A) or poly(U) to the tetrapeptides induces larger delta E(0,0) and delta D than when bound to NCp7, indicating stronger stacking interactions. Poly(I), on the other hand, produces larger shifts in Trp37 of NCp7. Binding of rG(8) produces sequence-dependent effects in the peptides. When bound to NCp7, but in contrast with tetrapeptide binding, nucleic acids produce large changes in triplet state kinetics consistent with enhanced spin-orbit coupling. These results are discussed in terms of three limiting types of tryptophan-base interaction: intercalation, aromatic stacking, and edge-on interaction. These should have differing effects on the properties of the triplet state. 相似文献
123.
Structure of the VHS domain of human Tom1 (target of myb 1): insights into interactions with proteins and membranes 总被引:1,自引:0,他引:1
VHS domains are found at the N-termini of select proteins involved in intracellular membrane trafficking. We have determined the crystal structure of the VHS domain of the human Tom1 (target of myb 1) protein to 1.5 A resolution. The domain consists of eight helices arranged in a superhelix. The surface of the domain has two main features: (1) a basic patch on one side due to several conserved positively charged residues on helix 3 and (2) a negatively charged ridge on the opposite side, formed by residues on helix 2. We compare our structure to the recently obtained structure of tandem VHS-FYVE domains from Hrs [Mao, Y., Nickitenko, A., Duan, X., Lloyd, T. E., Wu, M. N., Bellen, H., and Quiocho, F. A. (2000) Cell 100, 447-456]. Key features of the interaction surface between the FYVE and VHS domains of Hrs, involving helices 2 and 4 of the VHS domain, are conserved in the VHS domain of Tom1, even though Tom1 does not have a FYVE domain. We also compare the structures of the VHS domains of Tom1 and Hrs to the recently obtained structure of the ENTH domain of epsin-1 [Hyman, J., Chen, H., Di Fiore, P. P., De Camilli, P., and Brünger, A. T. (2000) J. Cell Biol. 149, 537-546]. Comparison of the two VHS domains and the ENTH domain reveals a conserved surface, composed of helices 2 and 4, that is utilized for protein-protein interactions. In addition, VHS domain-containing proteins are often localized to membranes. We suggest that the conserved positively charged surface of helix 3 in VHS and ENTH domains plays a role in membrane binding. 相似文献
124.
The endoplasmic reticulum (ER) molecular chaperone, BiP, plays a role in the cotranslational translocation and subsequent
folding and assembly of newly synthesized proteins targeted to the ER and secretory pathway. The sequence encoding a Douglas-fir
(Pseudotsuga menziesii [Mirb] Franco) BiP homologue (PmBiP) was identified by differential screening of a seedling cDNA library. Southern blotting
indicated that PmBiP is most likely present as a single copy. The deduced amino acid sequence of PmBiP contains an HEEL tetrapeptide
sequence which functions to retain PmBiP in the ER and is different from HDEL commonly found in angiosperm plant BiPs. Amino
acid sequence alignment and phylogenetic analysis show that PmBiP is highly similar to other plant BiPs yet forms a distinct
phylogenetic subgroup which is separate from the angiosperm BiPs. Northern and western blotting revealed that PmBiP is subject
to developmental regulation during seed development, germination, and early seedling growth and is seasonally regulated in
needles of young seedlings.
Received: 21 February 2000 / Accepted: 13 April 2000 相似文献
125.
We have studied the translocation of cytosolic phospholipase A(2) (cPLA(2)) to nuclei in macrophages stimulated with receptor-recognized forms of alpha(2)-macroglobulin (alpha(2)M*). Translocation of phosphorylated cPLA(2) to nuclei was determined by immunoprecipitation of cPLA(2) in (32)P(i)-labeled cells. The identity of cPLA(2) was established by comparing its mobility on gels with an authentic cPLA(2) standard. cPLA(2) activity was quantified by measuring the release of [(14)C]arachidonic acid from the substrate 1-palmitoyl-2-[1-(14)C]arachidonyl-sn-glycerophosphatidylcholine. alpha(2)M* caused a two- to threefold increase in cPLA(2) phosphorylation and its translocation to nuclei. The p38 MAPK inhibitor SB203580, PKC inhibitor chelerythrin, or depletion of intracellular Ca(2+) profoundly decreased cPLA(2) activity in nuclei isolated from agonist-stimulated cells. The requirement for Ca(2+), PKC, and p38 MAPK activation appears to be of major importance for nuclear cPLA(2) activity. In contrast to cellular cPLA(2) activity, nuclear cPLA(2) activity was not inhibited by arachidonyl trifluoromethyl ketone (AACOCF(3)) in agonist-stimulated cells. It is concluded that the association of cPLA(2) with nuclear membranes in agonist-stimulated cells modifies the activity and the sensitivity of the enzyme to inhibition by AACOCF(3) in this phospholipid environment. 相似文献
126.
Asplin IR Misra UK Gawdi G Gonzalez-Gronow M Pizzo SV 《Archives of biochemistry and biophysics》2000,383(1):135-141
Cellular binding of receptor-recognized forms of alpha2-macroglobulin (alpha2M*) is mediated by the low-density lipoprotein receptor related protein (LRP) and the alpha2M signaling receptor (alpha2MSR). In nonmalignant cells, ligation of alpha2MSR promotes DNA synthesis and cellular proliferation. Here, we report that insulin treatment of highly metastatic 1-LN human prostate carcinoma selectively increases alpha2MSR expression and binding of alpha2M* to 1-LN cells. alpha2M* induces transient increases in intracellular calcium and inositol 1,4,5-trisphosphate in insulin-treated 1-LN cells, consistent with activation of alpha2MSR. Inhibition of signaling cascades activated by insulin blocks upregulation of alpha2MSR. By contrast, alpha2M* does not bind to nor induce intracellular signaling in PC-3 cells, even though 1-LN cells were subcloned from PC-3 cells. We suggest that alpha2M* behaves like a growth factor in these highly malignant cells. The 1-LN metastatic phenotype may result, in part, from aberrant expression of alpha2MSR, indicating the possible involvement of alpha2M* in tumor progression. 相似文献
127.
128.
129.
Screening and selection of media components for lactic acid production using Plackett–Burman design 总被引:2,自引:0,他引:2
S. Krishnan S. G. Prapulla D. Rajalakshmi M. C. Misra N. G. Karanth 《Bioprocess and biosystems engineering》1998,19(1):61-65
Plackett–Burman design was used to efficiently select important media components influencing lactic acid production in a two step screening procedure. A total of 36 screening experiments were conducted for studying the effect of various media components such as carbon and nitrogen (simple and complex) sources, minerals/buffering agents and a specific inducer for the production of lactic acid by Lactobacillus plantarum NCIM 2084. The eleven ingredients chosen after the first screening experiments were further screened by a Plackett-Burman design consisting of 12 experiments. Liquefied starch, wheat bran extract, ammonium nitrate, manganese sulphate and sodium acetate were chosen as promising ingredients for further optimisation studies. The highest yield of 41.9?g/l of lactic acid was obtained at the end of 24 hours of fermentation which corresponded to 90% conversion, on the basis of sugar supplied. 相似文献
130.