全文获取类型
收费全文 | 1346篇 |
免费 | 100篇 |
国内免费 | 1篇 |
出版年
2024年 | 3篇 |
2023年 | 4篇 |
2022年 | 14篇 |
2021年 | 34篇 |
2020年 | 19篇 |
2019年 | 23篇 |
2018年 | 29篇 |
2017年 | 32篇 |
2016年 | 34篇 |
2015年 | 82篇 |
2014年 | 75篇 |
2013年 | 92篇 |
2012年 | 112篇 |
2011年 | 95篇 |
2010年 | 57篇 |
2009年 | 57篇 |
2008年 | 75篇 |
2007年 | 63篇 |
2006年 | 70篇 |
2005年 | 55篇 |
2004年 | 79篇 |
2003年 | 41篇 |
2002年 | 48篇 |
2001年 | 20篇 |
2000年 | 17篇 |
1999年 | 9篇 |
1998年 | 15篇 |
1997年 | 12篇 |
1996年 | 13篇 |
1995年 | 7篇 |
1994年 | 9篇 |
1993年 | 6篇 |
1992年 | 14篇 |
1991年 | 14篇 |
1990年 | 11篇 |
1989年 | 10篇 |
1988年 | 13篇 |
1987年 | 7篇 |
1986年 | 3篇 |
1985年 | 6篇 |
1984年 | 7篇 |
1983年 | 7篇 |
1982年 | 8篇 |
1981年 | 5篇 |
1980年 | 4篇 |
1979年 | 9篇 |
1978年 | 6篇 |
1977年 | 5篇 |
1975年 | 3篇 |
1974年 | 7篇 |
排序方式: 共有1447条查询结果,搜索用时 375 毫秒
51.
52.
Carina Johansson Anders Pedersen B G?ran Karlsson Jan Rydstr?m 《European journal of biochemistry》2002,269(18):4505-4515
Membrane-bound transhydrogenases are conformationally driven proton-pumps which couple an inward proton translocation to the reversible reduction of NADP+ by NADH (forward reaction). This reaction is stimulated by an electrochemical proton gradient, Delta p, presumably through an increased release of NADPH. The enzymes have three domains: domain II spans the membrane, while domain I and III are hydrophilic and contain the binding sites for NAD(H) and NADP(H), respectively. Separately expressed domain I and III together catalyze a very slow forward reaction due to tightly bound NADP(H) in domain III. With the aim of examining the mechanistic role(s) of loop D and E in domain III and intact cysteine-free Escherichia coli transhydrogenase by cysteine mutagenesis, the conserved residues beta A398, beta S404, beta I406, beta G408, beta M409 and beta V411 in loop D, and residue beta Y431 in loop E were selected. In addition, the previously made mutants betaD392C and betaT393C in loop D, and beta G430C and beta A432C in loop E, were included. All loop D and E mutants, especially beta I406C and beta G430C, showed increased ratios between the rates of the forward and reverse reactions, thus approaching that of the wild-type enzyme. Determination of values indicated that the former increase was due to a strongly increased dissociation of NADPH caused by an altered conformation of loops D and E. In contrast, the cysteine-free G430C mutant of the intact enzyme showed the same inhibition of both forward and reverse rates. Most domain III mutants also showed a decreased affinity for domain I. The results support an important and regulatory role of loops D and E in the binding of NADP(H) as well as in the interaction between domain I and domain III. 相似文献
53.
Page R Moy K Sims EC Velasquez J McManus B Grittini C Clayton TL Stevens RC 《BioTechniques》2004,37(3):364, 366, 368 passim
54.
Schwarzenbacher R Jaroszewski L von Delft F Abdubek P Ambing E Biorac T Brinen LS Canaves JM Cambell J Chiu HJ Dai X Deacon AM DiDonato M Elsliger MA Eshagi S Floyd R Godzik A Grittini C Grzechnik SK Hampton E Karlak C Klock HE Koesema E Kovarik JS Kreusch A Kuhn P Lesley SA Levin I McMullan D McPhillips TM Miller MD Morse A Moy K Ouyang J Page R Quijano K Robb A Spraggon G Stevens RC van den Bedem H Velasquez J Vincent J Wang X West B Wolf G Xu Q Hodgson KO Wooley J Wilson IA 《Proteins》2004,55(3):759-763
55.
Schwarzenbacher R von Delft F Jaroszewski L Abdubek P Ambing E Biorac T Brinen LS Canaves JM Cambell J Chiu HJ Dai X Deacon AM DiDonato M Elsliger MA Eshagi S Floyd R Godzik A Grittini C Grzechnik SK Hampton E Karlak C Klock HE Koesema E Kovarik JS Kreusch A Kuhn P Lesley SA Levin I McMullan D McPhillips TM Miller MD Morse A Moy K Ouyang J Page R Quijano K Robb A Spraggon G Stevens RC van den Bedem H Velasquez J Vincent J Wang X West B Wolf G Xu Q Hodgson KO Wooley J Wilson IA 《Proteins》2004,56(2):392-395
56.
Extensive manufacturing of explosives in the last century has resulted in widespread contamination of soils and waters. Decommissioning and cleanup of these materials has also led to concerns about the explosive hazards associated with residual energetics still present on the surfaces of ordnance and explosives scrap. Typically, open burning or detonation is used to decontaminate ordinance and explosive scrap. Here the use of an anaerobic microbiological system applied as a bioslurry to decontaminate energetics from the surfaces of metal scrap is described. Decontamination of model metal scrap artificially contaminated with 2,4,6-trinitrotoluene and of decommissioned mortar rounds still containing explosives residue was examined. A portable ion mobility spectrometer was employed for the detection of residual explosives residues on the surfaces of the scrap. The mixed microbial populations of the bioslurries effectively decontaminated both the scrap and the mortar rounds. Use of the ion mobility spectrometer was an extremely sensitive field screening method for assessing decontamination and is a method by which minimally trained personnel can declare scrap clean with a high level of certainty. 相似文献
57.
58.
Dysfunction in various parts of immune defence, such as immune response, immune complex clearance, and inflammation, has an
impact on pathogenesis in systemic lupus erythematosus (SLE). We hypothesised that combinations of common variants of genes
involved in these immune functions are associated with susceptibility to SLE. The following variants were analysed: HLA DR3,
HLA DQ2, C4AQ0, Fcγ receptor IIa (FcγRIIa) genotype R/R, Fcγ receptor IIIa (FcRγIIIa) genotype F/F, mannan-binding lectin
(MBL) genotype conferring a low serum concentration of MBL (MBL-low), and interleukin-1 receptor antagonist (IL-1Ra) genotype
2/2. Polymorphisms were analysed in 143 Caucasian patients with SLE and 200 healthy controls. HLA DR3 in SLE patients was
in 90% part of the haplotype HLA DR3-DQ2-C4AQ0, which was strongly associated with SLE (odds ratio [OR] 2.8, 95% CI 1.7–4.5).
Analysis of combinations of gene variants revealed that the strong association with SLE for HLA DR3-DQ2-C4AQ0 remained after
combination with FcγRIIa R/R, FcγRIIIa F/F, and MBL-low (OR>2). Furthermore, the combination of the FcγRIIa R/R and IL-1Ra
2/2 genotypes yielded a strong correlation with SLE (OR 11.8, 95% CI 1.5–95.4). This study demonstrates that certain combinations
of gene variants may increase susceptibility to SLE, suggesting this approach for future studies. It also confirms earlier
findings regarding the HLA DR3-DQ2-C4AQ0 haplotype. 相似文献
59.
Lindeberg J Usoskin D Bengtsson H Gustafsson A Kylberg A Söderström S Ebendal T 《Genesis (New York, N.Y. : 2000)》2004,40(2):67-73
Catecholaminergic neurons are affected in several neurological and psychiatric diseases. Tyrosine hydroxylase (TH) is the first, rate-limiting enzyme in catecholamine synthesis. We report a knockin mouse expressing Cre-recombinase from the 3'-untranslated region of the endogenous Th gene by means of an internal ribosomal entry sequence (IRES). The resulting Cre expression matches the normal pattern of TH expression, while the pattern and level of TH are not altered in the knockin mouse. Crossings with two different LacZ reporter mice demonstrated Cre-mediated genomic recombination in TH expressing tissues. In addition, LacZ was found in some unexpected cell populations (including oocytes), indicating recombination due to transient developmental TH expression. Our novel knockin mouse can be used for generation of tissue-specific or general knockouts (depending on scheme of crossing) in mice carrying genes flanked by loxP sites. This knockin mouse can also be used for tracing cell lineages expressing TH during development. 相似文献
60.
Multi-modality imaging identifies key times for annexin V imaging as an early predictor of therapeutic outcome 总被引:2,自引:0,他引:2
Mandl SJ Mari C Edinger M Negrin RS Tait JF Contag CH Blankenberg FG 《Molecular imaging》2004,3(1):1-8
Radiolabeled annexin V may provide an early indication of the success or failure of anticancer therapy on a patient-by-patient basis as an in vivo marker of tumor cell killing. An important question that remains is when, after initiation of treatment, should annexin V imaging be performed. To address this issue, we obtained simultaneous in vivo measurements of tumor burden and uptake of radiolabeled annexin V in the syngeneic orthotopic murine BCL1 lymphoma model using in vivo bioluminescence imaging (BLI) and small animal single-photon emission computed tomography (SPECT). BCL1 cells labeled for fluorescence and bioluminescence assays (BCL1-gfp/luc) were injected into mice at a dose that leads to progressive disease within two to three weeks. Tumor response was followed by BLI and SPECT before and after treatment with a single dose of 10 mg/kg doxorubicin. Biodistribution analyses revealed a biphasic increase of annexin V uptake within the tumor-bearing tissues of mice. An early peak occurring before actual tumor cells loss was observed between 1 and 5 hr after treatment, and a second longer sustained rise from 9 to 24 hr after therapy, which heralds the onset of tumor cell loss as confirmed by BLI. Multimodality imaging revealed the temporal patterns of tumor cell loss and annexin V uptake revealing a better understanding of the timing of radiolabeled annexin V uptake for its development as a marker of therapeutic efficacy. 相似文献