全文获取类型
收费全文 | 889篇 |
免费 | 93篇 |
国内免费 | 1篇 |
专业分类
983篇 |
出版年
2021年 | 8篇 |
2018年 | 8篇 |
2017年 | 7篇 |
2016年 | 10篇 |
2015年 | 20篇 |
2014年 | 26篇 |
2013年 | 35篇 |
2012年 | 28篇 |
2011年 | 33篇 |
2010年 | 22篇 |
2009年 | 22篇 |
2008年 | 35篇 |
2007年 | 23篇 |
2006年 | 32篇 |
2005年 | 35篇 |
2004年 | 25篇 |
2003年 | 26篇 |
2002年 | 26篇 |
2001年 | 25篇 |
2000年 | 22篇 |
1999年 | 19篇 |
1998年 | 15篇 |
1997年 | 15篇 |
1996年 | 16篇 |
1994年 | 12篇 |
1993年 | 11篇 |
1992年 | 17篇 |
1991年 | 14篇 |
1990年 | 17篇 |
1989年 | 15篇 |
1988年 | 27篇 |
1987年 | 10篇 |
1986年 | 19篇 |
1985年 | 11篇 |
1983年 | 8篇 |
1982年 | 13篇 |
1980年 | 11篇 |
1979年 | 21篇 |
1978年 | 18篇 |
1977年 | 8篇 |
1976年 | 15篇 |
1974年 | 10篇 |
1973年 | 19篇 |
1972年 | 23篇 |
1971年 | 20篇 |
1970年 | 20篇 |
1969年 | 16篇 |
1968年 | 10篇 |
1967年 | 8篇 |
1966年 | 7篇 |
排序方式: 共有983条查询结果,搜索用时 0 毫秒
1.
Timothy J. French Anthony W. Good T. Norman Palmer Mary C. Sugden 《Bioscience reports》1985,5(9):729-734
The in vivo effects of dexamethasone administration on liver and extrahepatic tissue carnitine concentrations were assessed in 48-h-starved rats. In heart and kidney, but not in liver, dexamethasone significantly increased total carnitine concentration. Acute (2.5 h) treatment with 2-tetradecylglycidate (TDG), a specific inhibitor of carnitine palmitoyl transferase 1, not only increased total hepatic carnitine concentrations, but also permitted an effect of dexamethasone (a further increase in hepatic carnitine concentration). The results are discussed in terms of acute (substrate-mediated) and chronic (hormonal) control of carnitine turnover. 相似文献
2.
The aggregation of amyloid-β protein (Aβ) in vivo is a critical pathological event in Alzheimer's disease. Although more and more evidence shows that the intermediate oligomers are the primary neurotoxic species in Alzheimer's disease, the particular structural features responsible for the toxicity of these intermediates are poorly understood. We measured the peptide level solvent accessibility of multiple Aβ(1-40) aggregated states using hydrogen exchange detected by mass spectrometry. A gradual reduction in solvent accessibility, spreading from the C-terminal region to the N-terminal region was observed with ever more aggregated states of Aβ peptide. The observed hydrogen exchange protection begins with reporter peptides 20-34 and 35-40 in low molecular weight oligomers found in fresh samples and culminates with increasing solvent protection of reporter peptide 1-16 in long time aged fibrillar species. The more solvent exposed structure of intermediate oligomers in the N-termini relative to well-developed fibrils provides a novel explanation for the structure-dependent neurotoxicity of soluble oligomers reported previously. 相似文献
3.
The 230-kDa gamete surface protein of Plasmodium falciparum is also a target for transmission-blocking antibodies 总被引:14,自引:0,他引:14
I A Quakyi R Carter J Rener N Kumar M F Good L H Miller 《Journal of immunology (Baltimore, Md. : 1950)》1987,139(12):4213-4217
Immunization with extracellular sexual stages of the malaria parasites can induce the production of antibodies which block the development of the parasites in the midgut of a mosquito after a blood meal. We have generated a number of monoclonal antibodies against gametes and zygotes of the human malaria Plasmodium falciparum. Two monoclonal antibodies (mAb) reacting with a 230-kDa gamete surface protein (mAb 1B3 and 2B4 both isotype IgG2a) were found to block transmission of P. falciparum to mosquitoes. Blocking was complement dependent and this was verified in vitro by the rapid lysis of newly formed gametes and zygotes in the presence of the mAb and active complement. Both mAb reacted by immunofluorescence with the surface of gametes and zygotes from isolates of P. falciparum from various geographical areas. Each mAb immunoprecipitated a 230-kDa protein from 125I-labeled surface proteins of newly formed gametes and zygotes and immunoblotted a protein doublet of about molecular mass 260 and 230 kDa from gametocytes and gametes of P. falciparum. Only the 230-kDa protein is expressed on the surface of newly formed macrogametes and zygotes. The 230-kDa gamete surface protein forms a molecular complex with two proteins of 48 and 45 kDa. The 48- and 45-kDa gamete surface proteins have previously been shown to be targets of mAb which block infectivity of P. falciparum to mosquitoes. The present study now demonstrates that antibodies against the 230-kDa gamete surface protein block transmission of P. falciparum to mosquitoes. The 230-kDa gamete protein is thus a potential candidate for a gamete vaccine. 相似文献
4.
5.
Recombinant human IL-2 overcomes genetic nonresponsiveness to malaria sporozoite peptides. Correlation of effect with biologic activity of IL-2 总被引:5,自引:0,他引:5
M F Good D Pombo M N Lunde W L Maloy R Halenbeck K Koths L H Miller J A Berzofsky 《Journal of immunology (Baltimore, Md. : 1950)》1988,141(3):972-977
Current malaria vaccine strategies focus on subunit vaccines that contain one or a limited number of malaria Ag. However, there is widespread nonresponsiveness to many of these Ag probably resulting from Ir gene control. Using a congenic mouse model, we demonstrated that human rIL-2 (as an adjuvant) can overcome Ir gene controlled low immune responsiveness to peptide malaria Ag vaccine candidates [R32tet32, R32LR, and Th2R-NP (NANP)5NA] as determined by the antibody response, providing it is emulsified with the Ag during immunization. This effect is not caused by IL-2 merely acting as a foreign protein and stimulating noncognate help; it requires biologic activity of the IL-2, as determined by studying the effect of inactive rIL-2, which has minimal biologic activity but which has retained its antigenicity. IL-2 does not appear to be working by an effect on priming of specific Th, and IL-2 cannot overcome an Ir gene controlled low T cell proliferative response. IL-2 may have a role to play in human vaccine development where a high titer antibody response to a subunit vaccine is required. 相似文献
6.
Cat thymocytes, bone marrow cells, and peripheral blood leukocytes (PBL) formed rosettes with guinea pig (GP) and gerbil (G) erythrocytes (E). In PBL from adult cats the frequency of rosettes was 27% with GPE and GE, while an average of 33% bone marrow cells formed rosettes with GPE and only 4% with GE. Thymocytes from kittens showed a high percentage of rosettes with both GPE and GE (35 to 81%), with the frequency of each type varying with the thymus tested. Fluorescein isothiocyanate labeling of one of the erythrocyte species revealed these cells to be rosetting with different nucleated cells; i.e., a low percentage (3-5%) of the rosettes formed with PBL and bone marrow had both labeled and unlabeled erythrocytes. In contrast, "mixed" rosettes were observed with a significant number of thymocytes, averaging 33% of thymocytes from six animals. A further distinction between the GE- and GPE-rosetting cells was revealed by a monoclonal antibody which blocked GE rosette formation without interfering with the binding of GPE to PBL and thymocytes. PBL could be depleted of either GPE- or GE-rosetting cells, with retention of IgG+ cells and cells capable of rosetting with the second erythrocyte species in the nonrosetting fractions. Stimulation of the latter nonrosetting fractions with pokeweed mitogen for induction of Ig synthesis revealed a T-lymphocyte specificity of the GE- and GPE-rosetting cells. PBL depleted of GE-rosetting cells yielded an increased Ig production, two- to threefold above the control; in contrast, depletion of GPE-rosetting cells from PBL resulted in a failure of the remaining cells to respond. These results suggest that T-suppressor cells of the cat are contained in the GE-rosetting fraction and T-helper cells are rosetted with GPE. 相似文献
7.
A theory is presented on the solubility of proteins, in the hydrated as well as in the dry state, and in water as well as in organic solvents. To this effect, colloidal stability is assimilated with the solubility of the proteins, considered as hydrated entities. By means of a surface thermodynamic approach it can be shown that an increase in size of a hydrated protein must lead to insolubility, even in the absence of any change in a protein's surface properties. This can be substantiated experimentally by comparing the surface properties of immune complexes with those of their constituent immunoglobulins, as well as by comparing some of the properties of intact tobacco mosaic virus with those of its monomeric capsid subunits. Insolubilization of proteins by means of charge interactions as well as by dehydration is studied; an explanation is given of why precipitation caused by charge interactions is more likely to lead to partial irreversible denaturation than precipitation caused by protein-protein interactions brought about by partial dehydration (e.g., by “salting-out”). A link is established between the smallness (or even the negative value) of the interfacial tension between given proteins and various solvents and their solubility in these solvents. The energy of hydration of proteins can also be measured, and the differences between the free energies of interaction of dried and hydrated proteins with water point toward the additional processes underlying the solubilization, i.e., toward the conformational change of a protein in the process of becoming hydrated. The parameter of conformational change of a protein, while becoming hydrated, appears to be more closely linked to its degree of hydration than to its hydration energy. 相似文献
8.
Biochemical pathways in prokaryotes can be traced backward through evolutionary time 总被引:10,自引:0,他引:10
For the first time, a credible prokaryotic phylogenetic tree is being
assembled by Woese and others using quantitative sequence analysis of
oligonucleotides in the highly conservative rRNA. This provides an
evolutionary scale against which the evolutionary steps that led to the
arrangement and regulation of contemporary biochemical pathways can be
measured. This paper presents an emerging evolutionary picture of aromatic
amino acid biosynthesis within a large superfamily assemblage of
prokaryotes that is sufficiently developed to illustrate a new perspective
that will be applicable to many other biochemical pathways.
相似文献
9.
10.