全文获取类型
收费全文 | 668篇 |
免费 | 82篇 |
出版年
2021年 | 6篇 |
2019年 | 7篇 |
2018年 | 6篇 |
2017年 | 8篇 |
2016年 | 19篇 |
2015年 | 25篇 |
2014年 | 38篇 |
2013年 | 39篇 |
2012年 | 40篇 |
2011年 | 40篇 |
2010年 | 24篇 |
2009年 | 34篇 |
2008年 | 31篇 |
2007年 | 29篇 |
2006年 | 34篇 |
2005年 | 35篇 |
2004年 | 29篇 |
2003年 | 22篇 |
2002年 | 18篇 |
2001年 | 33篇 |
2000年 | 32篇 |
1999年 | 22篇 |
1998年 | 18篇 |
1997年 | 13篇 |
1996年 | 7篇 |
1995年 | 6篇 |
1994年 | 7篇 |
1993年 | 2篇 |
1992年 | 12篇 |
1991年 | 13篇 |
1990年 | 11篇 |
1989年 | 4篇 |
1988年 | 2篇 |
1987年 | 12篇 |
1986年 | 9篇 |
1985年 | 3篇 |
1984年 | 5篇 |
1983年 | 2篇 |
1982年 | 2篇 |
1981年 | 2篇 |
1979年 | 4篇 |
1978年 | 4篇 |
1976年 | 4篇 |
1975年 | 2篇 |
1972年 | 2篇 |
1971年 | 6篇 |
1970年 | 5篇 |
1969年 | 5篇 |
1968年 | 3篇 |
1967年 | 4篇 |
排序方式: 共有750条查询结果,搜索用时 468 毫秒
21.
M Krieger T Brunner S C Bischoff V von Tscharner A Walz B Moser M Baggiolini C A Dahinden 《Journal of immunology (Baltimore, Md. : 1950)》1992,149(8):2662-2667
IL-8 and its structural analogs derived from blood platelets have been proposed as stimuli of IgE-independent basophil activation. In order to clarify the mechanism of action of these peptides, we examined the effects of pure IL-8, connective tissue-activating peptide III (CTAP-III), neutrophil-activating peptide 2 (NAP-2), and platelet factor 4 (PF-4) on blood basophils with and without pretreatment by IL-3, which modulates mediator release. After pretreatment with IL-3, significant histamine release was observed with 10(-8) M and 10(-7) M IL-8 and 10(-7) M NAP-2, but not with the other peptides. At higher concentrations (10(-6) M), however, all IL-8 analogs, as well as the unrelated cationic peptides poly-D-lysine, histone VS, and lysozyme, induced histamine release to variable degrees. Binding and competition studies with [125I]IL-8 revealed specific IL-8R on basophils from a patient with chronic myelogenous leukemia and normal individuals. From 3500 to 9600 receptors with a mean Kd value of 0.15 nM were found on average per chronic myelogenous leukemia and normal basophil, respectively. NAP-2 weakly competed for IL-8 binding. IL-8 and, to a lesser extent, NAP-2 led to a transient rise of cytosolic free calcium concentration ([Ca2+]i), which was independent of a preexposure to IL-3. IL-8 prevented the [Ca2+]i rise induced by NAP-2, but did not influence [Ca2+]i responses to other agonists, e.g. C5a, C3a, or platelet-activating factor. IL-8 induced [Ca2+]i changes and histamine release in IL-3-primed basophils were pertussis toxin sensitive. CTAP-III or PF-4 did not compete for IL-8 binding, did not induce [Ca2+]i changes, and did not influence the [Ca2+]i response to IL-8 and NAP-2. This study shows that IL-8 and NAP-2 activate human basophils by a receptor-mediated mechanism similar to that operating in neutrophils. At high concentrations histamine release can also be induced by cationic peptides by a mechanism that does not involve the IL-8R, and probably depends on cationic interactions. 相似文献
22.
Wild-type p53 restores cell cycle control and inhibits gene amplification in cells with mutant p53 alleles. 总被引:113,自引:0,他引:113
Loss of cell cycle control and acquisition of chromosomal rearrangements such as gene amplification often occur during tumor progression, suggesting that they may be correlated. We show here that the wild-type p53 allele is lost when fibroblasts from patients with the Li-Fraumeni syndrome (LFS) are passaged in vitro. Normal and LFS cells containing wild-type p53 arrested in G1 when challenged with the uridine biosynthesis inhibitor PALA and did not undergo PALA-selected gene amplification. The converse occurred in cells lacking wild-type p53 expression. Expression of wild-type p53 in transformants of immortal and tumor cells containing mutant p53 alleles restored G1 control and reduced the frequency of gene amplification to undetectable levels. These studies reveal that p53 contributes to a metabolically regulated G1 check-point, and they provide a model for understanding how abnormal cell cycle progression leads to the genetic rearrangements involved in tumor progression. 相似文献
23.
The effect of neurotensin on submaximally-stimulated hepatobiliary and pancreatic secretion was studied in 6 healthy subjects. An intravenous infusion of neurotensin 1.4 ± 0.3 pmol/kg/min, designed to reproduce plasma neurotensin immunoreactivity levels within the physiological range, produced a significant increase in pancreatic bicarbonate output. Plasma concentrations of pancreatic polypeptide rose by 83 ± 16 pmol/l and were associated with a small reduction in trypsin, but no significant change in bilirubin outputs. 相似文献
24.
Isolation, characterization, and expression of cDNA encoding a rat liver endoplasmic reticulum alpha-mannosidase 总被引:6,自引:0,他引:6
We have isolated a cDNA encoding an endoplasmic reticulum alpha-mannosidase, an asparagine-linked oligosaccharide processing enzyme, from a rat liver lambda gt11 library. Two degenerate oligonucleotides, based on amino acid sequence data from the purified enzyme, were used as primers in the polymerase chain reaction with liver cDNA as a template to generate an unambiguous cDNA probe. The cDNA fragment (524 base pair) obtained was then used to isolate cDNA clones by hybridization. We isolated two overlapping clones which were used to construct a full-length cDNA of 3392 base pairs. A single open reading frame of 1040 amino acids encodes a protein with a molecular mass of 116 kilodaltons containing the six known peptide sequences. The deduced amino acid sequence revealed no classical signal sequence or membrane-spanning domain. The alpha-mannosidase encoding cDNA can be expressed transiently in COS cells using the mammalian expression vector pXM, causing a 400-fold increase in alpha-mannosidase activity as well as a dramatic increase in immunoreactive polypeptide. The rat liver endoplasmic reticulum alpha-mannosidase bears striking homology to the vacuolar alpha-mannosidase from Saccharomyces cerevisiae. 相似文献
25.
Fate of intravenously administered UDPglucose 总被引:2,自引:0,他引:2
E Bischoff M Liersch D Keppler K Decker 《Hoppe-Seyler's Zeitschrift für physiologische Chemie》1970,351(6):729-736
26.
Food Biophysics - The stabilization of interfaces with mixed emulsifiers composed of natural ingredients is of increasing interest in order to modulate stability of food colloids. To this purpose,... 相似文献
27.
James V. McCann Steven R. Bischoff Yu Zhang Dale O. Cowley Veronica Sanchez‐Gonzalez George D. Daaboul Andrew C. Dudley 《Genesis (New York, N.Y. : 2000)》2020,58(7)
Extracellular vesicles (EVs) are abundant, lipid‐enclosed vectors that contain nucleic acids and proteins, they can be secreted from donor cells and freely circulate, and they can be engulfed by recipient cells thus enabling systemic communication between heterotypic cell types. However, genetic tools for labeling, isolating, and auditing cell type‐specific EVs in vivo, without prior in vitro manipulation, are lacking. We have used CRISPR‐Cas9‐mediated genome editing to generate mice bearing a CD63‐emGFPloxP/stop/loxP knock‐in cassette that enables the specific labeling of circulating CD63+ vesicles from any cell type when crossed with lineage‐specific Cre recombinase driver mice. As proof‐of‐principle, we have crossed these mice with Cdh5‐CreERT2 mice to generate CD63emGFP+ vasculature. Using these mice, we show that developing vasculature is marked with emerald GFP (emGFP) following tamoxifen administration to pregnant females. In adult mice, quiescent vasculature and angiogenic vasculature (in tumors) is also marked with emGFP. Moreover, whole plasma‐purified EVs contain a subpopulation of emGFP+ vesicles that are derived from the endothelium, co‐express additional EV (e.g., CD9 and CD81) and endothelial cell (e.g., CD105) markers, and they harbor specific miRNAs (e.g., miR‐126, miR‐30c, and miR‐125b). This new mouse strain should be a useful genetic tool for generating cell type‐specific, CD63+ EVs that freely circulate in serum and can subsequently be isolated and characterized using standard methodologies. 相似文献
28.
29.
W-V Meister S. I. Kargov E. Birch-Hirschfeld C. Bohley G. Burckhardt G. Bischoff 《Nucleosides, nucleotides & nucleic acids》2013,32(9-11):1905-1913
Abstract A potential DNA triple helix of 21-mer oligodeoxyribonucleotides was synthesized and characterized. The strands were chosen to study the interaction of internal guide and intervening sequences analogs as well as adjacent 3′and 5′exon parts around the splicing site of Tetrahymena pre-rRNA. Further in parallel works a series of different RNA and DNA strands was synthesized and combined yielding a suitable order of stability. Here we want to show an isolated examination of a DNA-strand triple helix with defined sequences containing a central mismatched base arrangement and T-A-T bases at the ends. 相似文献