全文获取类型
收费全文 | 2950篇 |
免费 | 156篇 |
专业分类
3106篇 |
出版年
2022年 | 22篇 |
2021年 | 30篇 |
2020年 | 19篇 |
2019年 | 32篇 |
2018年 | 44篇 |
2017年 | 45篇 |
2016年 | 79篇 |
2015年 | 111篇 |
2014年 | 111篇 |
2013年 | 207篇 |
2012年 | 213篇 |
2011年 | 193篇 |
2010年 | 120篇 |
2009年 | 115篇 |
2008年 | 182篇 |
2007年 | 183篇 |
2006年 | 182篇 |
2005年 | 163篇 |
2004年 | 150篇 |
2003年 | 135篇 |
2002年 | 127篇 |
2001年 | 27篇 |
2000年 | 19篇 |
1999年 | 29篇 |
1998年 | 25篇 |
1997年 | 32篇 |
1996年 | 27篇 |
1995年 | 27篇 |
1994年 | 23篇 |
1993年 | 29篇 |
1992年 | 26篇 |
1991年 | 25篇 |
1990年 | 27篇 |
1989年 | 16篇 |
1988年 | 23篇 |
1987年 | 18篇 |
1986年 | 17篇 |
1985年 | 16篇 |
1984年 | 27篇 |
1983年 | 24篇 |
1982年 | 19篇 |
1981年 | 16篇 |
1980年 | 20篇 |
1979年 | 19篇 |
1978年 | 21篇 |
1977年 | 11篇 |
1976年 | 10篇 |
1975年 | 10篇 |
1974年 | 9篇 |
1973年 | 12篇 |
排序方式: 共有3106条查询结果,搜索用时 15 毫秒
101.
Orazio Cantoni Giorgio Brandi Amedeo Albano Flaminio Cattabeni 《Free radical research》1995,22(3):275-283
Cystine markedly enhanced the cytotoxic response of Escherichia coli cells to concentrations of hydrogen peroxide resulting in mode one killing, but displayed little effect in mode two killed cells. The effect of cystine was concentration-dependent over a range of 5-50 μM and did not further increase at higher levels. Cystine had similar effects in other bacterial systems.
In order to sensitize the cells to the oxidative injury, the amino acid must be present during exposure to the oxidant since no enhancement of the cytotoxic response can be observed in cystine pre-loaded cells. In addition, no further enhancement of cytotoxicity could be detected when cystine was added before and left during challenge with the oxidant. The enhancing effect of cystine on oxidative injury of E. coli cells appears to be directly mediated by the amino acid and in fact cysteic acid, the most likely oxidation product, had no effect on the killing of bacterial cells elicited by hydrogen peroxide. Other disulfide compounds such as oxidized glutathione, cystamine and dithionitrobenzoic acid only slightly increased the susceptibility of bacteria to the oxidant. The effect of the disulfides was not concentration-dependent over a range of 200-800 μM and was statistically significant only for cystamine.
Taken together, these results indicate that cystine markedly increases the cytotoxic response of bacteria to hydrogen peroxide and suggest that the amino acid might impair the cellular defence machinery against hydrogen peroxide. This effect may involve a thiol-disulfide exchange reaction at the cell membrane level. 相似文献
In order to sensitize the cells to the oxidative injury, the amino acid must be present during exposure to the oxidant since no enhancement of the cytotoxic response can be observed in cystine pre-loaded cells. In addition, no further enhancement of cytotoxicity could be detected when cystine was added before and left during challenge with the oxidant. The enhancing effect of cystine on oxidative injury of E. coli cells appears to be directly mediated by the amino acid and in fact cysteic acid, the most likely oxidation product, had no effect on the killing of bacterial cells elicited by hydrogen peroxide. Other disulfide compounds such as oxidized glutathione, cystamine and dithionitrobenzoic acid only slightly increased the susceptibility of bacteria to the oxidant. The effect of the disulfides was not concentration-dependent over a range of 200-800 μM and was statistically significant only for cystamine.
Taken together, these results indicate that cystine markedly increases the cytotoxic response of bacteria to hydrogen peroxide and suggest that the amino acid might impair the cellular defence machinery against hydrogen peroxide. This effect may involve a thiol-disulfide exchange reaction at the cell membrane level. 相似文献
102.
Enrico Teardo Elisabetta Bergantino Fernanda Rigoni Giorgio Mario Giacometti 《BBA》2007,1767(6):703-711
The PsbS subunit of Photosystem II (PSII) has received much attention in the past few years, given its crucial role in photoprotection of higher plants. The exact location of this small subunit in thylakoids is also debated. In this work possible interaction partners of PsbS have been identified by immunoaffinity and immunoprecipitation, performed with mildly solubilized whole thylakoid membrane. The interacting proteins, as identified by mass spectrometry analysis of the immunoaffinity eluate, include CP29, some LHCII components, but also components of Photosystem I, of the cytochrome b6f complex as well as of ATP synthase. These proteins can be co-immunoprecipitated by using highly specific anti-PsbS antibodies and, vice-versa, PsbS is co-immunoprecipitated by antisera against components of the interacting complexes. We also find that PsbS co-migrates with bands containing PSII, ATP synthase and cytochrome b6f as well as with LHCII-containing bands on non-denaturing Deriphat PAGE. These results suggest multiple location of PsbS in the thylakoid membrane and point to an unexpected lateral mobility of this PSII subunit. As revealed by immunogold labelling with antibody against PsbS, the protein is associated either with granal membranes or prevalently with stroma lamellae in low or high-intensity light-treated intact leaves, respectively. This finding is consistent with the capability of PsbS to interact with complexes located in stroma lamellae, even though the exact physiological condition(s) under which these interactions may take place remain to be clarified. 相似文献
103.
104.
Graziella Bellone Massimo Geuna Anna Carbone Stefania Silvestri Robin Foa Giorgio Emanuelli Lina Matera 《Journal of cellular physiology》1995,163(2):221-231
The pituitary hormone prolactin (Prl) is known to act as a local regulator of immune cell function, and Prl-binding receptors (Prl-R) have been described to share distinctive features with the members of the newly described cytokine/hemopoietin receptor superfamily. Here we show that the hormone can functionally interact with lineage-specific hemopoietic factors. When highly purified progenitor cells (CD34+ve) were seeded in semisolid methylcellulose cultures in the presence of interleukin (IL)-3, granulocyte-macrophage colony stimulating factor (GM-CSF), and erythropoietin (Epo), a selective enhancing effect of Prl on the formation of colony forming unit-granulocyte (CFU-G) and burst forming unit-erythroid (BFU-E) colonies was observed. The effect of the hormone was plotted as a bell shaped curve, with the optimal response at the supraphysiological concentration of 50 ng/ml. Limiting dilution analysis showed that Prl acted directly on hemopoietic progenitors. This was confirmed by the observation on the CD34+ve cells of Prl-binding sites reacting with the specific monoclonal antibodies (mAbs), U5 and PrR-7A. Immunoprecipitation of the metabolically labeled CD34+ve cells with the PrR-7A mAb revealed a structure of 43 kD under reducing conditions. Analysis of the early events associated with the Prl/Prl-R interaction showed an increased number of cells engaged in DNA and hemoglobin synthesis. Enhanced erythroid differentiation of CD34+ve cells in the presence of Prl was secondary to upmodulation of receptors for the lineage-specific factor Epo. Together these data demonstrate the existence of a functional interplay between Prl. and hemopoietic factors. © 1995 Wiley-Liss, Inc. 相似文献
105.
Evolution and functional characterization of the RH50 gene from the ammonia-oxidizing bacterium Nitrosomonas europaea 总被引:1,自引:0,他引:1 下载免费PDF全文
Cherif-Zahar B Durand A Schmidt I Hamdaoui N Matic I Merrick M Matassi G 《Journal of bacteriology》2007,189(24):9090-9100
The family of ammonia and ammonium channel proteins comprises the Amt proteins, which are present in all three domains of life with the notable exception of vertebrates, and the homologous Rh proteins (Rh50 and Rh30) that have been described thus far only in eukaryotes. The existence of an RH50 gene in bacteria was first revealed by the genome sequencing of the ammonia-oxidizing bacterium Nitrosomonas europaea. Here we have used a phylogenetic approach to study the evolution of the N. europaea RH50 gene, and we show that this gene, probably as a component of an integron cassette, has been transferred to the N. europaea genome by horizontal gene transfer. In addition, by functionally characterizing the Rh50Ne protein and the corresponding knockout mutant, we determined that NeRh50 can mediate ammonium uptake. The RH50Ne gene may thus have replaced functionally the AMT gene, which is missing in the genome of N. europaea and may be regarded as a case of nonorthologous gene displacement. 相似文献
106.
Vincent Oliéric Philippe Wolff Akiko Takeuchi Guillaume Bec Catherine Birck Marc Vitorino Bruno Kieffer Artemy Beniaminov Giorgio Cavigiolio Elizabeth Theil Christine Allmang Alain Krol Philippe Dumas 《Biochimie》2009
Selenocysteine (Sec) is co-translationally incorporated into selenoproteins at a reprogrammed UGA codon. In mammals, this requires a dedicated machinery comprising a stem-loop structure in the 3′ UTR RNA (the SECIS element) and the specific SECIS Binding Protein 2. In this report, disorder-prediction methods and several biophysical techniques showed that ca. 70% of the SBP2 sequence is disordered, whereas the RNA binding domain appears to be folded and functional. These results are consistent with a recent report on the role of the Hsp90 chaperone for the folding of SBP2 and other functionally unrelated proteins bearing an RNA binding domain homologous to SBP2. 相似文献
107.
Ausiello CM Fedele G Palazzo R Spensieri F Ciervo A Cassone A 《Microbes and infection / Institut Pasteur》2006,8(3):714-720
Infection, in particular by Chlamydia pneumoniae (Cp), has been associated with atherosclerosis and coronary heart disease. Immune reactions to heat shock proteins (HSPs) have been advocated to link infection to atherosclerosis and its acute sequelae based on molecular mimicry with host HSPs. We have here evaluated the role played by recombinant Cp-HSP60 and Cp-HSP10 for their ability to induce maturation of human monocyte-derived dendritic cells (MDDC) and T cell polarization. Cp-HSP60, but not Cp-HSP10, induced a strong MDCC maturation, as assessed by the expression of co-stimulatory molecules and other markers. Secretion of regulatory cytokines and enhancement of antigen presenting ability of mature (m)MDDC toward a clear T helper (Th) 1 pattern were also induced by Cp-HSP60. An analysis of the IL-12 cytokine family demonstrated that Cp-HSP60-matured MDDC were able to express p35 and p40 mRNA subunits to form IL-12, and p19 and p40 subunits to form IL-23. Thus, preferential Th1 polarization of immune response induced by Cp-HSP60-matured MDDC appears to be due to the concomitant expression of IL-12 and IL-23. Our data suggest that Cp-HSP60-matured DC may contribute to T-cell mediated immunopathology of atherosclerosis via a chronic stimulation of Th1 immune responses. 相似文献
108.
Gametogenesis of intergroup hybrids of hemiclonal frogs 总被引:1,自引:0,他引:1
Ragghianti M Bucci S Marracci S Casola C Mancino G Hotz H Guex GD Plötner J Uzzell T 《Genetical research》2007,89(1):39-45
European water frog hybrids Rana esculenta (R. ridibundaxR. lessonae) reproduce hemiclonally, by hybridogenesis: in the germ line they exclude the genome of one parental species and produce haploid gametes with an unrecombined genome of the other parental species. In the widespread L-E population system, both sexes of hybrids (E) coexist with R. lessonae (L). They exclude the lessonae genome and produce ridibunda gametes. In the R-E system, hybrid males coexist with R. ridibunda (R); they exclude either their ridibunda or their lessonae genome and produce sperm with a lessonae or with a ridibunda genome or a mixture of both kinds of sperm. We examined 13 male offspring, 12 of which were from crosses between L-E system and R-E system frogs. All were somatically hybrid. With one exception, they excluded the lessonae genome in the germ line and subsequently endoreduplicated the ridibunda genome. Spermatogonial metaphases contained a haploid or a diploid number of ridibunda chromosomes, identified through in situ hybridization to a satellite DNA marker, and by spermatocyte I metaphases containing a haploid number of ridibunda bivalents. The exception, an F1 hybrid between L-E system R. lessonae and R-E system R. ridibunda, was not hybridogenetic, showed no genome exclusion, and evidenced a disturbed gametogenesis resulting from the combination of two heterospecific genomes. None of the hybridogenetic hybrids showed any cell lines excluding the ridibunda genome, the pattern most frequent in hybrids of the R-E system, unique to that system, and essential for its persistence. A particular combination of R-E system lessonae and R-E system ridibunda genomes seems necessary to induce the R-E system type of hemiclonal gametogenesis. 相似文献
109.
Blanco YC Farias AS Goelnitz U Lopes SC Arrais-Silva WW Carvalho BO Amino R Wunderlich G Santos LM Giorgio S Costa FT 《PloS one》2008,3(9):e3126
Background
Cerebral malaria (CM) is a syndrome characterized by neurological signs, seizures and coma. Despite the fact that CM presents similarities with cerebral stroke, few studies have focused on new supportive therapies for the disease. Hyperbaric oxygen (HBO) therapy has been successfully used in patients with numerous brain disorders such as stroke, migraine and atherosclerosis.Methodology/Principal Findings
C57BL/6 mice infected with Plasmodium berghei ANKA (PbA) were exposed to daily doses of HBO (100% O2, 3.0 ATA, 1–2 h per day) in conditions well-tolerated by humans and animals, before or after parasite establishment. Cumulative survival analyses demonstrated that HBO therapy protected 50% of PbA-infected mice and delayed CM-specific neurological signs when administrated after patent parasitemia. Pressurized oxygen therapy reduced peripheral parasitemia, expression of TNF-α, IFN-γ and IL-10 mRNA levels and percentage of γδ and αβ CD4+ and CD8+ T lymphocytes sequestered in mice brains, thus resulting in a reduction of blood-brain barrier (BBB) dysfunction and hypothermia.Conclusions/Significance
The data presented here is the first indication that HBO treatment could be used as supportive therapy, perhaps in association with neuroprotective drugs, to prevent CM clinical outcomes, including death. 相似文献110.
Bisetto E Picotti P Giorgio V Alverdi V Mavelli I Lippe G 《Journal of bioenergetics and biomembranes》2008,40(4):257-267
The role of the integral inner membrane subunit e in self-association of F0F1ATP synthase from bovine heart mitochondria was analyzed by in situ limited proteolysis, blue native PAGE/iterative SDS-PAGE, and LC-MS/MS. Selective degradation of subunit e, without disrupting
membrane integrity or ATPase capacity, altered the oligomeric distribution of F0F1ATP synthase, by eliminating oligomers and reducing dimers in favor of monomers. The stoichiometry of subunit e was determined
by a quantitative MS-based proteomics approach, using synthetic isotope-labelled reference peptides IAQL*EEVK, VYGVGSL*ALYEK,
and ELAEAQEDTIL*K to quantify the b, γ and e subunits, respectively. Accuracy of the method was demonstrated by confirming
the 1:1 stoichiometry of subunits γ and b. Altogether, the results indicate that the integrity of a unique copy of subunit
e is essential for self-association of mammalian F0F1ATP synthase.
Elena Bisetto and Paola Picotti contributed equally to this work. 相似文献