全文获取类型
收费全文 | 1215篇 |
免费 | 139篇 |
国内免费 | 2篇 |
出版年
2022年 | 9篇 |
2021年 | 15篇 |
2020年 | 7篇 |
2019年 | 15篇 |
2018年 | 18篇 |
2017年 | 23篇 |
2016年 | 29篇 |
2015年 | 45篇 |
2014年 | 47篇 |
2013年 | 42篇 |
2012年 | 65篇 |
2011年 | 54篇 |
2010年 | 49篇 |
2009年 | 42篇 |
2008年 | 51篇 |
2007年 | 64篇 |
2006年 | 49篇 |
2005年 | 43篇 |
2004年 | 50篇 |
2003年 | 46篇 |
2002年 | 37篇 |
2001年 | 49篇 |
2000年 | 51篇 |
1999年 | 26篇 |
1998年 | 26篇 |
1997年 | 22篇 |
1996年 | 21篇 |
1995年 | 14篇 |
1994年 | 14篇 |
1993年 | 19篇 |
1992年 | 27篇 |
1991年 | 27篇 |
1990年 | 19篇 |
1989年 | 17篇 |
1988年 | 19篇 |
1987年 | 11篇 |
1986年 | 14篇 |
1985年 | 18篇 |
1984年 | 11篇 |
1983年 | 12篇 |
1982年 | 7篇 |
1979年 | 9篇 |
1978年 | 10篇 |
1977年 | 11篇 |
1975年 | 14篇 |
1974年 | 9篇 |
1972年 | 6篇 |
1971年 | 8篇 |
1967年 | 6篇 |
1966年 | 8篇 |
排序方式: 共有1356条查询结果,搜索用时 46 毫秒
941.
L J Holland C Suksang A A Wall L R Roberts D R Moser A Bhattacharya 《The Journal of biological chemistry》1992,267(10):7053-7059
942.
K R Feingold I Staprans R A Memon A H Moser J K Shigenaga W Doerrler C A Dinarello C Grunfeld 《Journal of lipid research》1992,33(12):1765-1776
Hyperlipidemia frequently accompanies infectious diseases and may be due to increases in lipoprotein production or decreases in lipoprotein clearance. The administration of endotoxin (LPS) has been used to mimic infection and prior studies demonstrate that LPS produces hypertriglyceridemia. In the present study in rodents, the dose of LPS necessary to induce hyperlipidemia was orders of magnitude less than that necessary to induce shock and death. As little as 10 ng/100 g body weight induced hypertriglyceridemia and this increase in serum triglyceride levels occurred rapidly (78% increase at 2 h). At high doses of LPS (50 micrograms/100 g body weight), the clearance of triglyceride-rich lipoproteins was decreased. At low doses of LPS (100 ng/100 g body weight), triglyceride clearance was not altered but the hepatic secretion of triglyceride was increased. Low dose LPS stimulated hepatic de novo fatty acid synthesis and lipolysis, both of which provided a source of fatty acids for the increase in hepatic triglyceride production. High dose LPS did not increase hepatic fatty acid synthesis or peripheral lipolysis, and hepatic triglyceride secretion was not stimulated. Thus, low dose LPS produces hypertriglyceridemia by increasing hepatic lipoprotein production, while high dose LPS produces hypertriglyceridemia by decreasing lipoprotein catabolism. Administration of anti-tumor necrosis factor (TNF) antibodies or interleukin 1 (IL-1) receptor antagonist did not prevent the increase in serum triglyceride levels induced by LPS. However, anti-TNF antibodies and interleukin 1 receptor antagonist (IL-1ra) blocked the increase in serum triglycerides induced by TNF or IL-1, respectively. These data suggest that neither of these cytokines is absolutely required for the increase in serum triglycerides induced by LPS, raising the possibility that other cytokines, small molecular mediators, or LPS itself may play a crucial role. 相似文献
943.
The Min (multiple intestinal neoplasia) mutation: its effect on gut epithelial cell differentiation and interaction with a modifier system 总被引:24,自引:0,他引:24
下载免费PDF全文
![点击此处可从《The Journal of cell biology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Min is a fully penetrant dominant mutation that leads to the development of multiple intestinal adenomas throughout the duodenal-to-colonic axis. Min/+ C57BL6/J mice have an average life-span of 120 d. Multi-label immunocytochemical studies of these lesions demonstrate patches of differentiated enterocytes, and scattered enteroendocrine, goblet and Paneth cells. Expression of endogenous marker genes within these differentiated cells can be directly correlated with the position occupied by the adenoma along the duodenal-to-colonic axis and mirrors the regional differentiation of the normal gut epithelium. The presence of multiple lineages in adenomas together with their retention of spatial information suggests that tumorigenesis in Min/+ mice may be initiated in a multipotent stem cell normally located at the base of intestinal crypts. To study the time-dependent properties of these tumors, genetic conditions were sought in which Min/+ animals could survive for up to 300 d. Min is fully penetrant in hybrids with either AKR/J or MA/MyJ. However, the hybrids demonstrate a reduction in the number of intestinal adenomas. Preliminary backcross analysis is consistent with a single major modifier locus unlinked to Min in both the AKR/J and MA/MyJ strains. The increased lifespan of the hybrid animals is also associated with the development of invasive tumors. New tumors do not arise continuously over the lifespan of these animals; instead all adenomas appear to be established by 100 d of age or sooner. These studies indicate that the Min/+ mouse is a powerful model system for analyzing the mechanisms that establish and maintain a balance between proliferation and differentiation in the continuously renewing gut epithelium and for an assessment of the multi-step hypothesis of intestinal neoplasia. 相似文献
944.
M J Santos S Hoefler A B Moser H W Moser P B Lazarow 《Journal of cellular physiology》1992,151(1):103-112
Empty membrane ghosts of peroxisomes were found in fibroblasts from a patient with Zellweger's syndrome, a genetic disease of humans (Santos et al: Science 239:1536-1538, 1988). Import of soluble matrix proteins into the organelle was defective. We have now studied fibroblasts from seven patients representing five complementation groups of the syndrome (defined by complementation for peroxisome enzyme function). We find that empty peroxisome ghosts are present in all seven cell samples. Three patients, representing three complementation groups, give the same membrane pattern by immunofluorescence: few large ghosts. Three other patients, representing two complementation groups, give a second pattern: many large ghosts. The seventh patient's pattern is distinct. Thus, all seven of these patients exhibit Peroxisome IMport (PIM) mutations. Since membrane assembly occurs in these cells, the results indicate that biogenesis of organelle content and membrane proteins proceed by different mechanisms. Growth and division of the empty peroxisomal membrane must occur, but are modified by the mutations (ghost size and abundance vary). Cell fusion and immunofluorescence analyses of peroxisome size and catalase packaging formally demonstrate genetic complementation groups for peroxisome assembly in Zellweger syndrome. 相似文献
945.
M Moser R Crameri G Menz T Schneider T Dudler C Virchow M Gmachl K Blaser M Suter 《Journal of immunology (Baltimore, Md. : 1950)》1992,149(2):454-460
Aspergillus fumigatus secretes an 18-kDa nonglycosylated IgE-binding protein. This protein was previously shown to be a ribotoxin, like alpha-sarcin and mitogillin. A 686-bp long A. fumigatus cDNA encoding an 18-kDa ribotoxin was cloned and expressed in Escherichia coli as a fusion protein with six adjacent histidines (rAsp f I/a). rAsp f I/a was purified to homogeneity by Ni(2+)-chelate affinity chromatography and refolded. The recombinant protein was enzymatically active resulting in the cleavage of 28S rRNA within a universally conserved region. rAsp f I/a was cytotoxic for EBV immortalized or PHA stimulated human PBMC. Furthermore, rAsp f I/a was recognized by murine mAb made against an 18-kDa ribotoxin. IgE of individuals allergic to A. fumigatus bound to rAsp f I/a as shown by ELISA, dot blots, and Western blots. rAsp f I/a elicited positive immediate type I skin reactions in individuals allergic to A. fumigatus but not in healthy control individuals. The results show that rAsp f I/a has similar functional characteristics when compared to the native 18-kDa ribotoxin. rAsp f I/a expressed in E. coli can therefore be used as a standardized Ag/allergen for serologic and clinical diagnosis of A. fumigatus-associated diseases. 相似文献
946.
McMurdo Sound, Antarctica, is suited for the study of the effects of eutrophication on diet-related parasites of Trematomus bernacchii (Boulenger, 1902) (Pisces). It has been relatively well studied, the environment is predictable, and there are significant differences in primary productivity over small distances. The differences in parasitism for 5 helminth species can be attributed to the enrichment processes in the sound. The prevalences of the acanthocephalan Echinorhynchus sp., the nematode Ascarophis nototheniae, the digenean Dinosoma sp., and the cestode Phyllobothrium sp. are significantly higher on the east side of the sound than on the west. The prevalence of the digenean Lepidepedon garrardi was significantly higher on the west side. We believe that the differences in the prevalences of infection between the east and west sides suggest that at least the benthic, adult fish do not readily move from one side of the sound to the other. We report the following (new host records are marked by asterisks): Echinorhynchus sp., Corynosoma hamanni (Acanthocephala); Phyllobothrium sp., Diphyllobothrium sp., Trypanorhyncha (Cestoidea); Clavellopsis (Copepoda); Dinosoma sp., Lepidepedon garrardi (Digenea); Pseudobenedenoides brachicola, Polyopisthocotylea (Monogenea); Contracaecum sp., Ascarophis nototheniae (Nematoda); Myxoproteus sp., Henneguya sp., Ceratomyxa sp., and Zschokkella sp. (Protozoa). 相似文献
947.
B Moser C Schumacher V von Tscharner I Clark-Lewis M Baggiolini 《The Journal of biological chemistry》1991,266(16):10666-10671
Neutrophil-activating peptide 1/interleukin 8 (NAP-1/IL-8), neutrophil-activating peptide 2 (NAP-2), and gro/melanoma growth-stimulatory activity (gro/MGSA) are potent inflammatory cytokines with homologous structure and similar neutrophil-activating properties. Receptors on human neutrophils that interact with these peptides were studied. Analysis of 125I-NAP-1/IL-8 binding at 0-4 degrees C revealed 64,500 +/- 14,000 receptors/cell with an apparent Kd of 0.18 +/- 0.07 nM (mean +/- S.D. of six independent experiments). Unlabeled NAP-1/IL-8, NAP-2, and gro/MGSA competed with 125I-NAP-1/IL-8 for binding to human neutrophils. Competition with increasing concentrations of unlabeled NAP-2 and gro/MGSA resolved two classes of NAP-1/IL-8 binding sites: about 70% of them bound NAP-2 and gro/MGSA with high affinity (Kd: 0.34 +/- 0.2 and 0.14 +/- 0.02), while 30% were of low affinity (Kd: 100 +/- 20 and 130 +/- 10 nM). Different binding sites, however, were not apparent upon competition with unlabeled NAP-1/IL-8, suggesting that both classes of receptors have similar affinities for NAP-1/IL-8. The existence of two receptors was also suggested by ligand cross-linking and cross-desensitization experiments. Two neutrophil membrane proteins with apparent Mr of 66,000-74,000 and 42,000-46,000 became cross-linked to 125I-NAP-1/IL-8, and the labeling was decreased when excess NAP-1/IL-8, NAP-2, or gro/MGSA was present. Stimulation of neutrophils with NAP-1/IL-8 resulted in desensitization toward a subsequent challenge with NAP-2 or gro/MGSA as shown by the rise in cytosolic free calcium. By contrast, following primary stimulation with NAP-2 or gro/MGSA, responses to NAP-1/IL-8 were only moderately attenuated, supporting the existence of NAP-1/IL-8 receptors which bind NAP-2 or gro/MGSA with low affinity. In conclusion, our results demonstrate that NAP-2 and gro/MGSA act upon human neutrophils by directly interacting with two classes of receptors for NAP-1/IL-8. 相似文献
948.
Anti-CD3 antibodies induce T cells from unprimed animals to secrete IL-4 both in vitro and in vivo 总被引:3,自引:0,他引:3
V Flamand D Abramowicz M Goldman C Biernaux G Huez J Urbain M Moser O Leo 《Journal of immunology (Baltimore, Md. : 1950)》1990,144(8):2875-2882
Recently, functional heterogeneity among Th cells has been recognized. Based on pattern of lymphokine secretion, two mutually exclusive subsets of CD4+ cells have been defined and designated Th1 (secreting IL-2 and IFN-gamma) and Th2 (secreting IL-4 and IL-5). Identification of these subsets was mostly based on the study of long term cultured T cell lines and clones, and little is known about the Th heterogeneity in vivo. In particular, it has been suggested that IL-4 producing cells cannot be detected in vivo or in primary stimulations in vitro unless responder cells had been previously primed. Our data however, indicate that anti-CD3 mediated stimulation can induce T cells isolated from unprimed animals to IL-4 production. An assay system based on the ability of IL-4 to increase Ia expression of B cells present in the environment of activated T cells was found to be more sensitive than detection of secreted IL-4 in the supernatant by conventional bioassays and was used to study IL-4 production by unprimed lymphocytes polyclonally stimulated in vivo and in vitro by anti-CD3 mAb. The results obtained indicate that CD4+ CD8- T cells able to produce IL-4 upon receptor-specific stimulation exist in the preimmune pool of adult animals. Remarkably, these cells can also be stimulated in vivo by treating animals with anti-CD3 mAb, as indicated by the in vivo induction of IL-4 specific mRNA and hyper-Ia expression on B cells. These results indicate that the inability to detect IL-4 in primary cultures is not due to different activation requirements of Th2 cells but may simply result from their lower frequency in unprimed animals. 相似文献
949.
Effect of tumor necrosis factor administration in vivo on lipoprotein lipase activity in various tissues of the rat 总被引:4,自引:0,他引:4
When added to murine adipocytes in culture, tumor necrosis factor (TNF) decreases the levels of lipoprotein lipase (LPL). Semb et al (1987. J. Biol Chem. 262: 8390-8394) have shown that administration of murine TNF to rats decreases lipoprotein lipase (LPL) in the epididymal fat pad with maximal inhibition requiring several hours. We have now tested the effects of treatment of rats with TNF on LPL activity in a variety of tissues and find that few show decreases in LPL under conditions that acutely increase serum triglycerides. Ninety minutes after treatment of male rats with human TNF (25 micrograms/200 g, i.v.), serum triglycerides rose 2.2-fold but there was no decrease in LPL activity in epididymal fat. Sixteen hours after TNF treatment LPL activity had decreased by 44% in epididymal fat, consistent with the previously reported data. In contrast, in female rats, no significant decrease was seen in LPL activity in parametrial adipose tissue at either 90 min or 16 hr after TNF administration despite increases in serum triglycerides (1.8-fold and 1.5-fold, respectively). There was little change in LPL activity in most other adipose tissue sites of male or female rats at either time after TNF treatment. No effect of TNF was seen on heart or diaphragm muscle LPL at any time. TNF treatment of both male and female rats produces consistent increases in de novo hepatic lipogenesis in vivo under conditions that increase serum triglycerides. It is unlikely that the limited effects of TNF on LPL in vivo can account for the rapid and sustained increase in serum triglycerides. 相似文献
950.
Moser KM 《The Western journal of medicine》1977,127(4):330-331
In 1974 in California, 72,645 patients were admitted to hospital for backache. In 50 percent of these patients there was a diagnosis compatible with discogenic disease. Surgical treatment was done in 27 percent of the patients admitted to hospital. Total figures were determined for hospital costs and the costs of physician-related services. Costs for surgical treatment exceeded medical costs. Extrapolated to a national scale, it appears that the national cost for patients in hospital because of backache in 1974 was $1.38 billion. This does not include outpatient care expense or loss of income. 相似文献