全文获取类型
收费全文 | 1881篇 |
免费 | 97篇 |
国内免费 | 143篇 |
出版年
2023年 | 31篇 |
2022年 | 72篇 |
2021年 | 77篇 |
2020年 | 56篇 |
2019年 | 80篇 |
2018年 | 67篇 |
2017年 | 45篇 |
2016年 | 33篇 |
2015年 | 47篇 |
2014年 | 99篇 |
2013年 | 217篇 |
2012年 | 72篇 |
2011年 | 113篇 |
2010年 | 84篇 |
2009年 | 74篇 |
2008年 | 84篇 |
2007年 | 113篇 |
2006年 | 79篇 |
2005年 | 80篇 |
2004年 | 61篇 |
2003年 | 51篇 |
2002年 | 47篇 |
2001年 | 34篇 |
2000年 | 34篇 |
1999年 | 36篇 |
1998年 | 28篇 |
1997年 | 22篇 |
1996年 | 17篇 |
1995年 | 24篇 |
1994年 | 20篇 |
1993年 | 18篇 |
1992年 | 12篇 |
1991年 | 17篇 |
1990年 | 11篇 |
1989年 | 7篇 |
1988年 | 11篇 |
1986年 | 5篇 |
1985年 | 12篇 |
1984年 | 30篇 |
1983年 | 11篇 |
1982年 | 20篇 |
1981年 | 12篇 |
1980年 | 8篇 |
1979年 | 8篇 |
1978年 | 6篇 |
1977年 | 4篇 |
1976年 | 7篇 |
1975年 | 5篇 |
1974年 | 6篇 |
1973年 | 6篇 |
排序方式: 共有2121条查询结果,搜索用时 109 毫秒
1.
J. Kelley Bentley Peter W. Reed 《Biochimica et Biophysica Acta (BBA)/General Subjects》1981,678(2):238-244
All of the common cytochalasins activate superoxide anion release and exocytosis of β-N-acetylglucosaminidase and lysozyme from guinea-pig polymorphonuclear leukocytes (neutrophils) incubated in a buffered sucrose medium. Half-maximal activation of both processes is produced by approx. 2 μM cytochalasin A, C >μM cytochalasin B ? 4–5 μM cytochalasin D, E. While maximal rates of O2? release and extents of exocytosis require extracellular calcium (1–2 mM), replacing sucrose with monovalent cation chlorides is inhibitory to neutrophil activation by cytochalasins. Na+, K+ or choline inhibited either cytochalasin B- or E-stimulated O2? production with IC50 values of 5–10 mM and inhibition occurs whether Cl?, NO3? or SCN? is the anion added with Na+ or K+. Release of β-N-acetylglucosaminidase in control or cytochalasin B-stimulated cells is inhibited by NaCl (IC50 ≈ 10 mM), while cytochalasin E-stimulated exocytosis is reduced less and K+ or choline chloride are ineffective in inhibiting either cytochalasin B- or E-stimulated exocytosis. Release of β-glucuronidase, myeloperoxidase or acid phosphatase from neutrophils incubated in buffered sucrose is not stimulated by cytochalasin B. Stimulation of either O2? or β-N-acetylglucosaminidase release by low concentrations of cytochalasin A is followed by inhibition of each at higher concentrations. It appears that all cytochalasins can activate both NAD(P)H oxidase and selective degranulation of neutrophils incubated in salt-restricted media and that differential inhibition of these two processes by monovalent cations and/or anions is produced at some step(s) subsequent to cytochalasin interaction with the cell. 相似文献
2.
Phytochemical analysis of dried twigs of Marsdenia roylei (family Asclepiadaceae) has resulted in the isolation of a trisaccharide, maryal, and a diglycoside, rolinose. Their structures were determined as O-beta-D-oleandropyranosyl-(1-->4)-O-beta-D-digitoxopyranosyl++ +-(1-->4)-D- cymaral and ethyl O-beta-D-oleandropyranosyl-(1-->4)-O-3-O-methyl-6-deoxy-beta-D- allopyranoside, respectively, by chemical degradation and spectroscopic methods. 相似文献
3.
Nataly Mancette Rijensky Netta R. Blondheim Shraga Eilon Barnea Nir Peled Eli Rosenbaum Aron Popovtzer Solomon M. Stemmer Alejandro Livoff Mark Shlapobersky Neta Moskovits Dafna Perry Eitan Rubin Itzhak Haviv Arie Admon 《Molecular & cellular proteomics : MCP》2020,19(8):1360-1374
- Download : Download high-res image (147KB)
- Download : Download full-size image
- •Sufficient tumor tissues are often unavailable large HLA peptidome discovery.
- •Using patient derived xenograft (PDX) tumors can overcome this limitation.
- •The large PDX HLA peptidomes expand significantly those of the original biopsies.
- •The HLA peptidomes of the PDX tumors included many tumor antigens.
4.
《Molecular & cellular proteomics : MCP》2023,22(2):100490
Aspergillus flavus is a common saprophytic and pathogenic fungus, and its secondary metabolic pathways are one of the most highly characterized owing to its aflatoxin (AF) metabolite affecting global economic crops and human health. Different natural environments can cause significant variations in AF synthesis. Succinylation was recently identified as one of the most critical regulatory post-translational modifications affecting metabolic pathways. It is primarily reported in human cells and bacteria with few studies on fungi. Proteomic quantification of lysine succinylation (Ksuc) exploring its potential involvement in secondary metabolism regulation (including AF production) has not been performed under natural conditions in A. flavus. In this study, a quantification method was performed based on tandem mass tag labeling and antibody-based affinity enrichment of succinylated peptides via high accuracy nano-liquid chromatography with tandem mass spectrometry to explore the succinylation mechanism affecting the pathogenicity of naturally isolated A. flavus strains with varying toxin production. Altogether, 1240 Ksuc sites in 768 proteins were identified with 1103 sites in 685 proteins quantified. Comparing succinylated protein levels between high and low AF-producing A. flavus strains, bioinformatics analysis indicated that most succinylated proteins located in the AF biosynthetic pathway were downregulated, which directly affected AF synthesis. Versicolorin B synthase is a key catalytic enzyme for heterochrome B synthesis during AF synthesis. Site-directed mutagenesis and biochemical studies revealed that versicolorin B synthase succinylation is an important regulatory mechanism affecting sclerotia development and AF biosynthesis in A. flavus. In summary, our quantitative study of the lysine succinylome in high/low AF-producing strains revealed the role of Ksuc in regulating AF biosynthesis. We revealed novel insights into the metabolism of AF biosynthesis using naturally isolated A. flavus strains and identified a rich source of metabolism-related enzymes regulated by succinylation. 相似文献
5.
Somayeh Najafi Dorcheh Soheila Rahgozar Daryush Talei 《Journal of cellular and molecular medicine》2021,25(13):6148-6160
Combination therapies, using medicinal herbs, are broadly recommended to attenuate the chemotherapy adverse effects. Based on our previous findings considering the anti-leukaemic effects of ginger extract on acute lymphoblastic leukaemia (ALL) cells, the present study was aimed to investigate the anti-cancer role of this pharmaceutical plant on ALL mice models. Moreover, we worked towards identifying the most anti-leukaemic derivative of ginger and the mechanism through which it may exert its cytotoxic impact. In vivo experiments were performed using five groups of six C57BL/6 nude mice, and the anti-leukaemic activity of ginger extract alone or in combination with methotrexate (MTX) was examined. Results showed increased survival rate and reduced damages in mice brain and liver tissues. Subsequently, MTT assay demonstrated synergistic growth inhibitory effect of 6-shogaol (6Sh) and MTX on ALL cell lines and patients primary cells. Eventually, the molecular anti-neoplastic mechanism of 6Sh was evaluated using Bioinformatics. Flow cytometry illustrated 6Sh-mediated apoptosis in Nalm-6 cells confirmed by Western blotting and RT-PCR assays. Further analyses exhibited the generation of reactive oxygen species (ROS) through 6Sh. The current study revealed the in vivo novel anti-leukaemic role of ginger extract, promoted by MTX. Moreover, 6-shogaol was introduced as the major player of ginger cytotoxicity through inducing p53 activity and ROS generation. 相似文献
6.
We previously reported on the in vitro antifungal activity of a crude whole plant extract from Eucomis autumnalis against seven economically important plant pathogenic fungi. A crude extract of the bulb showed similar in vitro mycelial growth inhibition of the same plant pathogenic fungi as well as that of an eighth fungus, Mycosphaerella pinodes, the cause of black spot or Ascochyta blight, in peas. Subsequently, fourth internode leaves were removed from 4 wk old pea plants, placed on moist filter paper in Petri dishes and inoculated with an M. pinodes spore suspension before and after treatment with the extract. The control of Ascochyta blight by different concentrations of the crude E. autumnalis extract was followed in vivo by leaf symptoms over a 6 day period at 20°C in a growth cabinet. The crude extract prevented M. pinodes spore infection of the leaves when the leaves were inoculated with spores both before or after treatment with the extract, confirming complete inhibition of spore germination. The crude E. autumnalis extract showed no phytotoxic reaction on the leaves even at the highest concentration applied. 相似文献
7.
Binding of chemoattractants to specific cell surface receptors on polymorphonuclear leukocytes (PMNs) initiates a series of biochemical responses leading to cellular activation. A critical early biochemical event in chemoattractant (CTX) receptor-mediated signal transduction is the phosphodiesteric cleavage of plasma membrane phosphatidylinositol 4,5-bisphosphate (PIP2), with concomitant production of the calcium mobilizing inositol-1,4,5-trisphosphate (IP3) isomer, and the protein kinase C activator, 1,2-diacylglycerol (DAG). The following lines of experimental evidence collectively suggest that CTX receptors are coupled to phospholipase C via a guanine nucleotide binding (G) protein. Receptor-mediated hydrolysis of PIP2 in PMN plasma membrane preparations requires both fMet-Leu-Phe and GTP, and incubation of intact PMNs with pertussis toxin (which ADP ribosylates and inactivates some G proteins) eliminates the ability of fMet-Leu-Phe plus GTP to promote PIP2 breakdown in isolated plasma membranes. Studies with both PMN particulate fractions and with partially purified fMet-Leu-Phe receptor preparations indicate that guanine nucleotides regulate CTX receptor affinity. Finally, fMet-Leu-Phe stimulates high-affinity binding of GTP gamma S to PMN membranes as well as GTPase activity. A G alpha subunit has been identified in phagocyte membranes which is different from other G alpha subunits on the basis of molecular weight and differential sensitivity to ribosylation by bacterial toxins. Thus, a novel G protein may be involved in coupling CTX receptors to phospholipase C. Studies in intact and sonicated PMNs demonstrate that metabolism of 1,4,5-IP3 proceeds via two distinct pathways: 1) sequential dephosphorylation to 1,4-IP2, 4-IP1 and inositol, or 2) ATP-dependent conversion to inositol 1,3,4,5-tetrakisphosphate (IP4) followed by sequential dephosphorylation to 1,3,4-IP3, 3,4-IP2, 3-IP1 and inositol. Receptor-mediated hydrolysis of PIP2 occurs at ambient intracellular Ca2+ levels; but metabolism of 1,4,5-IP3 via the IP4 pathway requires elevated cytosolic Ca2+ levels associated with cellular activation. Thus, the two pathways for 1,4,5-IP3 metabolism may serve different metabolic functions. Additionally, inositol phosphate production appears to be controlled by protein kinase C, as phorbol myristate acetate (PMA) abrogates PIP2 hydrolysis by interfering with the ability of the activated G protein to stimulate phospholipase C. This implies a physiologic mechanism for terminating biologic responses via protein kinase C mediated feedback inhibition of PIP2 hydrolysis. 相似文献
8.
Addition of fruit cell wall extracts from two muskmelon cultivars into liquid media affected mycotoxin production by a strain of Myrothecium roridum pathogenic to muskmelon. Cell wall extracts from a susceptible cultivar (Iroquois) significantly increased toxin production while cell wall extracts from a resistant cultivar (Hales Best) significantly inhibited toxin production. Media containing 0.1 or 1.0 mg ml–1 stimulated toxin production more than media containing 10 or 100 mg ml–1 of cell wall extracts. Previous studies in our laboratory suggest that roridin E may be involved in virulence or pathogenicity of M. roridum; the present study indicates that cell wall polysaccharides as well as other materials present in cell wall preparations from susceptible host tissue provide a better substrate for toxin production than cell wall preparation from resistant host tissue. 相似文献
9.
Slim-Eric Letaíef Grard Landemore Jean Bocquet Jacques Izard 《Biology of the cell / under the auspices of the European Cell Biology Organization》1989,65(3):257-263
This paper reports that the Kurloff cell sulphated and chondroitinase AC sensitive material previously described filtered on Sepharose CL4B columns as 2 main populations with Kav of 0.25 and 0.44. Its alkaline treatment resulted in the elution of 2 peaks with Kav of 0.52 and 0.78. Their reduction in size observed after alkaline treatment and the 6-fold increase in the (35S) sulphate incorporation after addition of 0.1 mM xyloside to the incubation medium indicate that these intracellular sulphated glycosaminoglycans exist in the form of proteoglycans. They were characterized by their resistance to degradation by pronase, papain or cathepsin D, as assessed by gel filtration chromatography on Sepharose CL6B or CL4B. After the glycosaminoglycans were digested with chondroitinase AC, thin-layer chromatography analysis indicated the presence of delta di-4S and delta di-6S in a ratio of 7:1. The presence of such protease-resistant proteochondroitin sulphate in intracytoplasmic granules of both Kurloff cells and other natural killer cell types is emphasized. 相似文献
10.
Summary Axillary bud expiants from South Pacific (Solomon Islands) taro, Colocasia esculenta var. esculenta cv. Akalomamale (Araceae) cultured on a modified Murashige-Skoog medium containing 1 mg NAA 1–1 and TE formed callus and produced multiple plantlets. Explants died if NAA was present at levels lower than 0.1 mg 1–1. BA was not required and may have been inhibitory. Plantlets developed faster and became larger following transfer to a hormone-free medium two weeks after the start of culture. Fully grown plants were established in a potting mix and are growing well in a greenhouse.Abbreviations BA
benzyladenine
- BM
basal medium
- Ca
Colocasia esculenta var. antiquorum
- Ce
Colocasia esculenta var. esculenta
- Ck
cytokinin(s)
- CW
coconut water
- HSMSM
half strength Murashige Skoog macroelements
- HSMS
half strength Murashige and Skoog medium
- IM
initial medium(ia)
- MS
Murashige and Skoog medium
- NAA
naphthaleneacetic acid
- SM
second medium
- TE
taro corm extract
- UCI
University of California, Irvine 相似文献