全文获取类型
收费全文 | 485篇 |
免费 | 30篇 |
专业分类
515篇 |
出版年
2023年 | 2篇 |
2022年 | 5篇 |
2021年 | 17篇 |
2020年 | 6篇 |
2019年 | 9篇 |
2018年 | 18篇 |
2017年 | 17篇 |
2016年 | 25篇 |
2015年 | 26篇 |
2014年 | 17篇 |
2013年 | 19篇 |
2012年 | 36篇 |
2011年 | 29篇 |
2010年 | 16篇 |
2009年 | 15篇 |
2008年 | 24篇 |
2007年 | 19篇 |
2006年 | 30篇 |
2005年 | 30篇 |
2004年 | 19篇 |
2003年 | 20篇 |
2002年 | 17篇 |
2001年 | 6篇 |
2000年 | 14篇 |
1999年 | 3篇 |
1998年 | 4篇 |
1996年 | 2篇 |
1994年 | 2篇 |
1993年 | 2篇 |
1992年 | 4篇 |
1991年 | 8篇 |
1990年 | 8篇 |
1989年 | 3篇 |
1988年 | 2篇 |
1987年 | 3篇 |
1986年 | 3篇 |
1985年 | 2篇 |
1984年 | 3篇 |
1979年 | 1篇 |
1978年 | 4篇 |
1976年 | 2篇 |
1975年 | 1篇 |
1974年 | 2篇 |
1972年 | 2篇 |
1971年 | 1篇 |
1970年 | 4篇 |
1968年 | 5篇 |
1967年 | 1篇 |
1966年 | 1篇 |
1965年 | 1篇 |
排序方式: 共有515条查询结果,搜索用时 15 毫秒
31.
Claudio Iribarren Viviana Hermosilla Violeta Morin Marcia Puchi 《Journal of cellular biochemistry》2013,114(8):1779-1788
In amphibians, sperm histone transition post‐fertilization during male pronucleus formation is commanded by histone chaperone Nucleoplasmin (NPM). Here, we report the first studies to analyze the participation of a Nucleoplasmin‐like protein on male chromatin remodeling in sea urchins. In this report, we present the molecular characterization of a nucleoplasmin‐like protein that is present in non fertilized eggs and early zygotes in sea urchin specie Tetrapygus niger. This protein, named MP62 can interact with sperm histones in vitro. By male chromatin decondensation assays and immunodepletion experiments in vitro, we have demonstrated that this protein is responsible for sperm nucleosome disorganization. Furthermore, as amphibian nucleoplasmin MP62 is phosphorylated in vivo immediately post‐fertilization and this phosphorylation is dependent on CDK‐cyclin activities found after fertilization. As we shown, olomoucine and roscovitine inhibits male nucleosome decondensation, sperm histone replacement in vitro and MP62 phosphorylation in vivo. This is the first report of a nucleoplasmin‐like activity in sea urchins participating during male pronucleus formation post‐fecundation. J. Cell. Biochem. 114: 1779–1788, 2013. © 2013 Wiley Periodicals, Inc. 相似文献
32.
Mayi TH Daoudi M Derudas B Gross B Bories G Wouters K Brozek J Caiazzo R Raverdi V Pigeyre M Allavena P Mantovani A Pattou F Staels B Chinetti-Gbaguidi G 《The Journal of biological chemistry》2012,287(26):21904-21913
Obesity is associated with a significantly increased risk for cancer suggesting that adipose tissue dysfunctions might play a crucial role therein. Macrophages play important roles in adipose tissue as well as in cancers. Here, we studied whether human adipose tissue macrophages (ATM) modulate cancer cell function. Therefore, ATM were isolated and compared with monocyte-derived macrophages (MDM) from the same obese patients. ATM, but not MDM, were found to secrete factors inducing inflammation and lipid accumulation in human T47D and HT-29 cancer cells. Gene expression profile comparison of ATM and MDM revealed overexpression of functional clusters, such as cytokine-cytokine receptor interaction (especially CXC-chemokine) signaling as well as cancer-related pathways, in ATM. Comparison with gene expression profiles of human tumor-associated macrophages showed that ATM, but not MDM resemble tumor-associated macrophages. Indirect co-culture experiments demonstrated that factors secreted by preadipocytes, but not mature adipocytes, confer an ATM-like phenotype to MDM. Finally, the concentrations of ATM-secreted factors related to cancer are elevated in serum of obese subjects. In conclusion, ATM may thus modulate the cancer cell phenotype. 相似文献
33.
Victor Manuel Duarte Zaragoza Rogelio Carrillo-González Maria Luisa Lozano Camargo Violeta Carrasco Hernández 《Soil & Sediment Contamination》2019,28(2):148-161
This study evaluated the effect of composted cow manure (CCM) on the chemical fractionation and retention degree of heavy metals (HMs) in mine tailings from Zimapán, México. In a greenhouse experiment, mine tailings from three deposits were incubated for 3 months; experimental units were placed in a PVC container, where increasing doses of CCM were applied. HM pseudo-total concentrations, HM extractions with ethylenediaminetetraacetic acid (EDTA, 0.05 M), and a sequential chemical extraction (SCE) were carried out. The HM concentrations were determined by atomic absorption spectrophotometry. The pseudo-total concentrations of Pb, Cu, Cd, and Ni found were up to 1506, 206, 27, and 23 mg kg?1, respectively; extractable Pb was up to 42%; 21% for Cu; 51% for Cd; and 16% of Ni of the pseudo-total concentrations of each metal. Treatment with 12% of CCM in mine tailing decreased EDTA-extractable HM concentrations, while the SCE revealed a decrease in exchangeable fraction and an increase in the organic fraction of HM. A positive correlation between CCM application and organic fractions of HMs was found, although the highest increasements were recorded in the organic fraction. 相似文献
34.
Markus K Muellner Barbara Mair Yasir Ibrahim Claudia Kerzendorfer Hannelore Lechtermann Claudia Trefzer Freya Klepsch André C Müller Ernestine Leitner Sabine Macho‐Maschler Giulio Superti‐Furga Keiryn L Bennett José Baselga Uwe Rix Stefan Kubicek Jacques Colinge Violeta Serra Sebastian MB Nijman 《Molecular systems biology》2015,11(2)
35.
Vladimirova NM Sautkina EN Ovchinnikova TV Potapenko NA 《Biochemistry. Biokhimii?a》2002,67(4):503-509
Functionally active Na2+,K2+-ATPase isozymes containing three types of the catalytic subunits (1, 2, and 3) were obtained from calf brain by two methods: selective removal of contaminating proteins according to Jorgensen (1974) and selective solubilization of the enzyme with subsequent reformation of the membrane structure according to Esmann (1988). All preparations were characterized with respect to ouabain-inhibition constants. The presence of the cytoskeleton protein tubulin (3 isoform) in the high-molecular-weight complex of Na2+,K2+-ATPase 31 isozyme from brain stem axolemma and the junction between Na2+,K2+-ATPase 3 subunit and tubulin 3 subunit are shown for the first time. 相似文献
36.
Lees CJ Apostolopoulos V Acres B Ong CS Popovski V McKenzie IF 《Cancer immunology, immunotherapy : CII》2000,48(11):644-652
MUC1 is a mucin over-expressed in breast cancer and a proposed target for immunotherapy. By immunising mice with MUC1 conjugated
to mannan (M-FP), CD8+ MHC-class-I restricted cytotoxic T lymphocytes (CTL), of high CTL precursor (CTLp) frequency (1/8000) and with significant
tumour protection, can be induced. The effect of various cytokines [interleukin-2 (IL-2), IL-4, IL-6, IL-7, interferon γ (IFNγ),
and granulocyte/macrophage-colony-stimulating factor (GM-CSF)] on the MUC1 CTL immune response was investigated (a) by measuring
the frequencies of CTLp in mice immunised with vaccinia virus constructs containing recombinant cytokines and M-FP, or (b)
by immunising cytokine- or cytokine-receptor-knockout (−/−) mice with M-FP. Vaccinia virus (VV) constructs containing recombinant
cytokines were used either individually or in combination in vivo with M-FP immunisation. M-FP immunisations combined with
VV-IL-2, VV-IL-7 and VV-GM-CSF, and combinations of VV-IFNγ + VV-IL-2, VV-IFNγ + VV-IL-4 or VV-GM-CSF + VV-IL-7 increased
CTLp frequencies up to threefold (1/17 666: M-FP + VV-GM-CSF + VV-IL-7) compared to M-FP (1/77 500) alone. By contrast, M-FP
combined with VV-IL-4 decreased the CTLp frequency threefold whereas VV-IL-6 and VV-IFNγ had no effect. Studies in cytokine-
and cytokine-receptor-gene-knockout (−/−) mice demonstrated that mice that are IL-2 −/− and IL-7 receptor −/− produce the
same CTLp response to M-FP as do control mice, whereas responses in the IL-6 −/−, IL-10 −/− and IFNγ−/− mice were marginally
improved and responses to M-FP in IL-4 −/− and tumour necrosis factor receptor 2 −/− mice were weaker. In spite of the increase
in CTLp frequency, this was not reflected in an in vivo tumour model. Tumour challenges using MUC1+ P815 cells, demonstrated that the addition of cytokines had little additive effect on the already effective tumour-regression
capabilities of M-FP alone.
Received: 24 September 1998 / Accepted: 21 September 1999 相似文献
37.
Fuel ethanol production from lignocellulosic materials is at a level where commercial biofuel production is becoming a reality. The solubilization of the hemicellulose fraction in lignocellulosic-based feedstocks results in a large variety of sugar mixtures including xylose. However, allowing xylose fermentation in yeast that normally is used for fuel ethanol production requires genetic engineering. Moreover, the efficiency of lignocellulosic pretreatment, together with the release and generation of inhibitory compounds in this step, are some of the new challenges faced during second generation ethanol production. Successful advances in all these aspects will improve ethanol yield, productivity and titer, which will reduce the impact on capital and operating costs, leading to the consolidation of the fermentation of lignocellulosic biomass as an economically feasible option for the production of renewable fuels. Therefore the development of yeast strains capable of fermenting a wide variety of sugars in a highly inhibitory environment, while maintaining a high ethanol yield and production rate, is required. This review provides an overview of the current status in the use of xylose-engineered yeast strains and describes the remaining challenges to achieve an efficient deployment of lignocellulosic-based ethanol production. 相似文献
38.
39.
Stanojevic V Habener JF Holz GG Leech CA 《Biochemical and biophysical research communications》2008,368(3):614-619
The role of adenylate kinase (AK) as a determinant of K-ATP channel activity in human pancreatic β-cells was investigated. We have identified that two cytosolic isoforms of AK, AK1 and AK5 are expressed in human islets and INS-1 cells. Elevated concentrations of glucose inhibit AK1 expression and AK1 immunoprecipitates with the Kir6.2 subunit of K-ATP. AK activation by ATP + AMP stimulates K-ATP channel activity and this stimulation is abolished by AK inhibitors. We propose that glucose stimulation of β-cells inhibits AK through glycolysis and also through the elevation of diadenosine polyphosphate levels. Glucose-dependent inhibition of AK increases the ATP/ADP ratio in the microenvironment of the K-ATP channel promoting channel closure and insulin secretion. The down-regulation of AK1 expression by hyperglycemia may contribute to the defective coupling of glucose metabolism to K-ATP channel activity in type 2 diabetes. 相似文献
40.