全文获取类型
收费全文 | 1073篇 |
免费 | 74篇 |
出版年
2023年 | 11篇 |
2022年 | 19篇 |
2021年 | 36篇 |
2020年 | 21篇 |
2019年 | 10篇 |
2018年 | 26篇 |
2017年 | 14篇 |
2016年 | 32篇 |
2015年 | 45篇 |
2014年 | 48篇 |
2013年 | 69篇 |
2012年 | 91篇 |
2011年 | 76篇 |
2010年 | 47篇 |
2009年 | 38篇 |
2008年 | 63篇 |
2007年 | 42篇 |
2006年 | 36篇 |
2005年 | 40篇 |
2004年 | 29篇 |
2003年 | 33篇 |
2002年 | 19篇 |
2001年 | 32篇 |
2000年 | 16篇 |
1999年 | 16篇 |
1998年 | 5篇 |
1997年 | 7篇 |
1996年 | 5篇 |
1995年 | 7篇 |
1994年 | 7篇 |
1993年 | 5篇 |
1992年 | 13篇 |
1991年 | 12篇 |
1990年 | 17篇 |
1989年 | 9篇 |
1988年 | 14篇 |
1987年 | 12篇 |
1986年 | 9篇 |
1985年 | 12篇 |
1984年 | 6篇 |
1982年 | 8篇 |
1981年 | 4篇 |
1980年 | 9篇 |
1979年 | 13篇 |
1978年 | 4篇 |
1973年 | 13篇 |
1972年 | 11篇 |
1971年 | 9篇 |
1970年 | 6篇 |
1966年 | 3篇 |
排序方式: 共有1147条查询结果,搜索用时 31 毫秒
991.
Phospholamban is a cardiac regulatory protein that, in its monomeric form, inhibits the Ca(2+)-ATPase. Lipid-protein interactions with a synthetic variant of phospholamban, in which all cysteine residues are replaced with alanine, have been studied by spin-label electron spin resonance (ESR) in different lipid host membranes. Both the stoichiometry and selectivity of lipid interactions were determined from the two-component ESR spectra of phospholipid species spin-labeled on the 14 C atom of the sn-2 chain. The lipid stoichiometry is determined by the oligomeric state of the protein and the selectivity by the membrane disposition of the positively charged residues in the N-terminal section of the protein. In dimyristoylphosphatidylcholine (DMPC) membranes, the stoichiometry (N(b)) is 7 lipids/monomer for the full-length protein and 4 for the transmembrane section (residues 26-52). These stoichiometries correspond to the dimeric and pentameric forms, respectively. In palmitoyloleoylphosphatidylcholine, N(b) = 4 for both the whole protein and the transmembrane peptide. In negatively charged membranes of dimyristoylphosphatidylglycerol (DMPG), the lipid stoichiometry is N(b) = 10-11 per monomer for both the full-length protein and the transmembrane peptide. This stoichiometry corresponds to monomeric dispersion of the protein in the negatively charged lipid. The sequence of lipid selectivity is as follows: stearic acid > phosphatidic acid > phosphatidylserine = phosphatidylglycerol = phosphatidylcholine > phosphatidylethanolamine for both the full-length protein and the transmembrane peptide in DMPC. Absolute selectivities are, however, lower for the transmembrane peptide. A similar pattern of lipid selectivity is obtained in DMPG, but the absolute selectivities are reduced considerably. The results are discussed in terms of the integration of the regulatory species in the lipid membrane. 相似文献
992.
993.
Rhesus macaque resistance to mucosal simian immunodeficiency virus infection is associated with a postentry block in viral replication 总被引:1,自引:0,他引:1
下载免费PDF全文
![点击此处可从《Journal of virology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
994.
995.
996.
The growth of red fibres in anterior and middle myotomal regions of B. sarana was mainly by hyperplasia in smaller size classes. In higher size classes, growth by hyperplasia was greater in posterior myotomal region compared to the other two myotomal regions. The growth of pink fibres in anterior myotomal regions was mainly by hypertrophy. The middle and posterior myotomal regions showed fibre growth by hyperplasia. The growth dynamics of white fibres revealed more or less similar pattern in all three myotomal regions against the somatic development. White fibres grew by hyperplasia up to 8 cm F.L. size classes and thereafter by hypertrophy. However, in > 12 cm F.L. size classes, the mean diameter of white fibres did not increase significantly. Similar pattern of growth was found in the white fibres of caudal fin muscle. It is interesting to note that the hyperplasia was mostly completed in the white fibres of the smallest fish studies, whereas, it continued to quite larger fish size in red and pink fibres. Thus, hyperplasia and hypertrophy may be responsible for growth in all fibre types in all myotomal regions in relation to somatic development in this small and medium growing species. 相似文献
997.
Zangeneh F Basu R Shah P Arora P Camilleri M Rizza RA 《American journal of physiology. Endocrinology and metabolism》2003,285(2):E280-E286
Portal infusion of glucose at rates approximating endogenous glucose production (EGP) causes paradoxical hypoglycemia in wild-type but not GLUT2 null mice, implying activation of a specific portal glucose sensor. To determine whether this occurs in humans, glucose containing [3-3H]glucose was infused intraduodenally at rates of 3.1 mg. kg-1. min-1 (n = 5), 1.55 mg. kg-1. min-1 (n = 9), or 0/0.1 mg. kg-1. min-1 (n = 9) for 7 h in healthy nondiabetic subjects. [6,6-2H2]glucose was infused intravenously to enable simultaneous measurement of EGP, glucose disappearance, and the rate of appearance of the intraduodenally infused glucose. Plasma glucose concentrations fell (P < 0.01) from 90 +/- 1 to 84 +/- 2 mg/dl during the 0/0.1 mg. kg-1. min-1 id infusions but increased (P < 0.001) to 104 +/- 5 and 107 +/- 3 mg/dl, respectively, during the 1.55 and 3.1 mg. kg-1. min-1 id infusions. In contrast, insulin increased (P < 0.05) during the 1.55 and 3.0 mg. kg-1. min-1 infusions, reaching a peak of 10 +/- 2 and 18 +/- 5 micro U/ml, respectively, by 2 h. Insulin concentrations then fell back to concentrations that no longer differed by study end (7 +/- 1 vs. 8 +/- 1 micro U/ml). This resulted in comparable suppression of EGP by study end (0.84 +/- 0.2 and 0.63 +/- 0.1 mg. kg-1. min-1). Glucose disappearance was higher (P < 0.01) during the final hour of the 3.1 than 1.55 mg. kg-1. min-1 id infusion (4.47 +/- 0.2 vs. 2.6 +/- 0.1 mg. kg-1. min-1), likely because of the slightly, but not significantly, higher glucose and insulin concentrations. We conclude that, in contrast to mice, selective portal glucose delivery at rates approximating EGP does not cause hypoglycemia in humans. 相似文献
998.
Wang J Fan J Laschinger C Arora PD Kapus A Seth A McCulloch CA 《The Journal of biological chemistry》2005,280(8):7273-7284
The mitogen-activated protein kinase p38 is activated by mechanical force, but the cellular elements that mediate force-induced p38 phosphorylation are not defined. As alpha-smooth muscle actin (SMA) is an actin isoform associated with force generation in fibroblasts, we asked if SMA participates in the activation of p38 by force. Tensile forces (0.65 pn/mum(2)) generated by magnetic fields were applied to collagen-coated magnetite beads bound to Rat-2 cells. Immunoblotting showed that p38alpha was the predominant p38 isoform. Analysis of bead-associated proteins demonstrated that SMA enrichment of collagen receptor complexes required the alpha2beta1 integrin. SMA was present almost entirely as filaments. Swinholide depolymerized SMA filaments and blocked force-induced p38 phosphorylation and force-induced increases of SMA. Knockdown of SMA (70% reduction) using RNA interference did not affect beta-actin but inhibited force-induced p38 phosphorylation by 50%. Inhibition of Rho kinase blocked SMA filament assembly, force-induced increases of SMA, and force-induced p38 activation. Force application increased SMA content and enhanced the association of phosphorylated p38 with SMA filaments. Blockade of p38 phosphorylation by SB203586 abrogated force-induced increases of SMA. In cells transfected with SMA promoter-beta-galactosidase fusion constructs, co-transfection with constitutively active p38 or MKK6 increased SMA promoter activity by 2.5-3-fold. Dominant negative p38 blocked force-induced activation of the SMA promoter. In SMA negative cells, there was no force-induced p38 phosphorylation. We conclude that force-induced p38 phosphorylation is dependent on an SMA filament-dependent pathway that uses a feed-forward amplification loop to synergize force-induced SMA expression with p38 activation. 相似文献
999.
Structural information for mammalian DNA pol-beta combined with molecular and essential dynamics studies have provided atomistically detailed views of functionally important conformational rearrangements that occur during DNA repair and replication. This conformational closing before the chemical reaction is explored in this work as a function of the bound substrate. Anchors for our study are available in crystallographic structures of the DNA pol-beta in "open" (polymerase bound to gapped DNA) and "closed" (polymerase bound to gapped DNA and substrate, dCTP) forms; these different states have long been used to deduce that a large-scale conformational change may help the polymerase choose the correct nucleotide, and hence monitor DNA synthesis fidelity, through an "induced-fit" mechanism. However, the existence of open states with bound substrate and closed states without substrates suggest that substrate-induced conformational closing may be more subtle. Our dynamics simulations of two pol-beta/DNA systems (with/without substrates at the active site) reveal the large-scale closing motions of the thumb and 8-kDa subdomains in the presence of the correct substrate--leading to nearly perfect rearrangement of residues in the active site for the subsequent chemical step of nucleotidyl transfer--in contrast to an opening trend when the substrate is absent, leading to complete disassembly of the active site residues. These studies thus provide in silico evidence for the substrate-induced conformational rearrangements, as widely assumed based on a variety of crystallographic open and closed complexes. Further details gleaned from essential dynamics analyses clarify functionally relevant global motions of the polymerase-beta/DNA complex as required to prepare the system for the chemical reaction of nucleotide extension. 相似文献
1000.
In calculations involving many displacements of an interacting pair of biomolecules, such as brownian dynamics, the docking of a substrate/ligand to an enzyme/receptor, or the screening of a large number of ligands as prospective inhibitors for a particular receptor site, there is a need for rapid evaluation of the desolvation penalties of the interacting pair. Although continuum electrostatic treatments with distinct dielectric constants for solute and solvent provide an account of the electrostatics of solvation and desolvation, it is necessary to re-solve the Poisson equation, at considerable computational cost, for each displacement of the interacting pair. We present a new method that uses a formulation of continuum electrostatic solvation in terms of the solvation energy density and approximates desolvation in terms of the occlusion of this density. We call it the SEDO approximation. It avoids the need to re-solve the Poisson equation, as desolvation is now estimated by an integral over the occluded volume. Test calculations are presented for some simple model systems and for some real systems that have previously been studied using the Poisson equation approach: MHC class I protein-peptide complexes and a congeneric series of human immunodeficiency virus type 1 (HIV-1) protease--ligand complexes. For most of the systems considered, the trends and magnitudes of the desolvation component of interaction energies obtained using the SEDO approximation are in reasonable correlation with those obtained by re-solving the Poisson equation. In most cases, the error introduced by the SEDO approximation is much less than that of the often-used test-charge approximation for the charge-charge components of intermolecular interactions. Proteins 2001;43:12-27. 相似文献