全文获取类型
收费全文 | 1541篇 |
免费 | 134篇 |
国内免费 | 2篇 |
专业分类
1677篇 |
出版年
2023年 | 8篇 |
2022年 | 23篇 |
2021年 | 42篇 |
2020年 | 26篇 |
2019年 | 23篇 |
2018年 | 39篇 |
2017年 | 28篇 |
2016年 | 54篇 |
2015年 | 112篇 |
2014年 | 99篇 |
2013年 | 111篇 |
2012年 | 188篇 |
2011年 | 148篇 |
2010年 | 89篇 |
2009年 | 61篇 |
2008年 | 101篇 |
2007年 | 93篇 |
2006年 | 80篇 |
2005年 | 65篇 |
2004年 | 70篇 |
2003年 | 59篇 |
2002年 | 42篇 |
2001年 | 7篇 |
2000年 | 7篇 |
1999年 | 10篇 |
1998年 | 9篇 |
1997年 | 7篇 |
1996年 | 4篇 |
1995年 | 9篇 |
1994年 | 10篇 |
1993年 | 4篇 |
1991年 | 5篇 |
1988年 | 2篇 |
1986年 | 7篇 |
1985年 | 4篇 |
1984年 | 4篇 |
1983年 | 3篇 |
1982年 | 2篇 |
1981年 | 1篇 |
1980年 | 1篇 |
1979年 | 3篇 |
1978年 | 1篇 |
1975年 | 3篇 |
1973年 | 2篇 |
1972年 | 2篇 |
1971年 | 1篇 |
1969年 | 2篇 |
1968年 | 1篇 |
1966年 | 1篇 |
1950年 | 1篇 |
排序方式: 共有1677条查询结果,搜索用时 15 毫秒
61.
Biological Effects of c-Mer Receptor Tyrosine Kinase in Hematopoietic Cells Depend on the Grb2 Binding Site in the Receptor and Activation of NF-κB 下载免费PDF全文
62.
63.
64.
65.
Schmid M Kindsmüller K Wimmer P Groitl P Gonzalez RA Dobner T 《Journal of virology》2011,85(14):7081-7094
The adenovirus type 5 (Ad5) E1B-55K and E4orf6 (E1B-55K/E4orf6) proteins are multifunctional regulators of Ad5 replication, participating in many processes required for virus growth. A complex containing the two proteins mediates the degradation of cellular proteins through assembly of an E3 ubiquitin ligase and induces shutoff of host cell protein synthesis through selective nucleocytoplasmic viral late mRNA export. Both proteins shuttle between the nuclear and cytoplasmic compartments via leucine-rich nuclear export signals (NES). However, the role of their NES-dependent export in viral replication has not been established. It was initially shown that mutations in the E4orf6 NES negatively affect viral late gene expression in transfection/infection complementation assays, suggesting that E1B-55K/E4orf6-dependent viral late mRNA export involves a CRM1 export pathway. However, a different conclusion was drawn from similar studies showing that E1B-55K/E4orf6 promote late gene expression without active CRM1 or functional NES. To evaluate the role of the E1B-55K/E4orf6 NES in viral replication in the context of Ad-infected cells and in the presence of functional CRM1, we generated virus mutants carrying amino acid exchanges in the NES of either or both proteins. Phenotypic analyses revealed that mutations in the NES of E1B-55K and/or E4orf6 had no or only moderate effects on viral DNA replication, viral late protein synthesis, or viral late mRNA export. Significantly, such mutations also did not interfere with the degradation of cellular substrates, indicating that the NES of E1B-55K or E4orf6 is dispensable both for late gene expression and for the activity associated with the E3 ubiquitin ligase. 相似文献
66.
Diana Walluscheck Kathrin Reissig Khuloud Bajbouj Oliver Ullrich Roland Hartig Hala Gali‐Muhtasib Antje Diestel Albert Roessner Regine Schneider‐Stock 《Journal of cellular and molecular medicine》2011,15(7):1528-1541
Besides the well‐understood DNA damage response via establishment of G2 checkpoint arrest, novel studies focus on the recovery from arrest by checkpoint override to monitor cell cycle re‐entry. The aim of this study was to investigate the role of Chk1 in the recovery from G2 checkpoint arrest in HCT116 (human colorectal cancer) wt, p53–/– and p21–/– cell lines following H2O2 treatment. Firstly, DNA damage caused G2 checkpoint activation via Chk1. Secondly, overriding G2 checkpoint led to (i) mitotic slippage, cell cycle re‐entry in G1 and subsequent G1 arrest associated with senescence or (ii) premature mitotic entry in the absence of p53/p21WAF1 causing mitotic catastrophe. We revealed subtle differences in the initial Chk1‐involved G2 arrest with respect to p53/p21WAF1: absence of either protein led to late G2 arrest instead of the classic G2 arrest during checkpoint initiation, and this impacted the release back into the cell cycle. Thus, G2 arrest correlated with downstream senescence, but late G2 arrest led to mitotic catastrophe, although both cell cycle re‐entries were linked to upstream Chk1 signalling. Chk1 knockdown deciphered that Chk1 defines long‐term DNA damage responses causing cell cycle re‐entry. We propose that recovery from oxidative DNA damage‐induced G2 arrest requires Chk1. It works as cutting edge and navigates cells to senescence or mitotic catastrophe. The decision, however, seems to depend on p53/p21WAF1. The general relevance of Chk1 as an important determinant of recovery from G2 checkpoint arrest was verified in HT29 colorectal cancer cells. 相似文献
67.
Continuous loss of CD4(+) T lymphocytes and systemic immune activation are hallmarks of untreated chronic HIV-1 infection. Chronic immune activation during HIV-1 infection is characterized by increased expression of activation markers on T cells, elevated levels of proinflammatory cytokines, and B cell hyperactivation together with hypergammaglobulinemia. Importantly, hyperactivation of T cells is one of the best predictive markers for progression toward AIDS, and it is closely linked to CD4(+) T cell depletion and sustained viral replication. Aberrant activation of T cells is observed mainly for memory CD4(+) and CD8(+) T cells and is documented, in addition to increased expression of surface activation markers, by increased cell cycling and apoptosis. Notably, the majority of these activated T cells are neither HIV specific nor HIV infected, and the antigen specificities of hyperactivated T cells are largely unknown, as are the exact mechanisms driving their activation. B cells are also severely affected by HIV-1 infection, which is manifested by major changes in B cell subpopulations, B cell hyperactivation, and hypergammaglobulinemia. Similar to those of T cells, the mechanisms underlying this aberrant B cell activation remain largely unknown. In this review, we summarized current knowledge about proposed antigen-dependent and -independent mechanisms leading to lymphocyte hyperactivation in the context of HIV-1 infection. 相似文献
68.
Captive breeding has become an important tool in species conservation programmes. Current management strategies for ex situ populations are based on theoretical models, which have mainly been tested in model species or assessed using studbook data.
During recent years an increasing number of molecular genetic studies have been published on captive populations of several
endangered species. However, a comprehensive analysis of these studies is still outstanding. Here, we present a review of
the published literature on ex situ conservation genetics with a focus on molecular studies. We analysed 188 publications which either presented empirical studies
using molecular markers (105), studbook analyses (26), theoretical work (38), or tested the genetic effects of management
strategies using model species (19). The results show that inbreeding can be minimized by a thorough management of captive
populations. There seems to be a minimum number of founders (15) and a minimum size of a captive population (100) necessary
in order to minimize a loss of genetic diversity. Optimally, the founders should be unrelated and new founders should be integrated
into the captive population successively. We recommend that genetic analyses should generally precede and accompany ex situ conservation projects in order to avoid inbreeding and outbreeding depression. Furthermore, many of the published studies
do not provide all the relevant parameters (founder size, captive population size, Ho, He, inbreeding coefficients). We, therefore, propose that a general standard for the presentation of genetic studies should
be established, which would allow integration of the data into a global database. 相似文献
69.
Elisabeth J. Leehr Kathrin Schag Amelie Brinkmann Ann-Christine Ehlis Andreas J. Fallgatter Stephan Zipfel Katrin E. Giel Thomas Dresler 《PloS one》2016,11(4)
ObjectiveFood stimuli are omnipresent and naturally primary reinforcing stimuli. One explanation for the intake of high amounts of food in binge eating disorder (BED) is a deviant valuation process. Valuation of food stimuli is supposed to influence approach or avoidance behaviour towards food. Focusing on self-reported and indirect (facial electromyography) valuation process, motivational aspects in the processing of food stimuli were investigated.MethodsWe compared an overweight sample with BED (BED+) with an overweight sample without BED (BED-) and with normal weight controls (NWC) regarding their self-reported and indirect (via facial electromyography) valuation of food versus non-food stimuli.ResultsRegarding the self-reported valuation, the BED+ sample showed a significantly stronger food-bias compared to the BED- sample, as food stimuli were rated as significantly more positive than the non-food stimuli in the BED+ sample. This self-reported valuation pattern could not be displayed in the indirect valuation. Food stimuli evoked negative indirect valuation in all groups. The BED+ sample showed the plainest approach-avoidance conflict marked by a diverging self-reported (positive) and indirect (negative) valuation of food stimuli.ConclusionsBED+ showed a deviant self-reported valuation of food as compared to BED-. The valuation process of the BED+ sample seems to be characterized by a motivational ambivalence. This ambivalence should be subject of further studies and may be of potential use for therapeutic interventions. 相似文献
70.
A novel pyrroloquinoline quinone dependent glucose dehydrogenase like enzyme (PQQ GDH) was isolated from Sorangium cellulosum So ce56. The putative coding region was cloned, over expressed in E. coli and the resulting enzyme was characterized. The recombinant protein has a relative molecular mass of 63 kDa and shows 43%
homology to PQQ GDH-B from Acinetobacter calcoaceticus. In the presence of PQQ and CaCl2 the enzyme has dehydrogenase activity with the substrate glucose as well as with other mono- and disaccharides. The thermal
stability and its pH activity profile mark the enzyme as a potential glucose biosensor enzyme. In order to decrease the activity
on maltose, which is unwanted for a potential application in biosensors, the protein was rationally modified at three specified
positions. The best variant showed a 59% reduction in activity on maltose compared to the wild type enzyme. The catalytic
efficiency (k
cat/K
M) was reduced fivefold but the specific activity still amounted to 63% of the wild type activity. 相似文献