全文获取类型
收费全文 | 1939篇 |
免费 | 134篇 |
专业分类
2073篇 |
出版年
2024年 | 1篇 |
2023年 | 6篇 |
2022年 | 22篇 |
2021年 | 29篇 |
2020年 | 23篇 |
2019年 | 51篇 |
2018年 | 45篇 |
2017年 | 43篇 |
2016年 | 73篇 |
2015年 | 112篇 |
2014年 | 110篇 |
2013年 | 145篇 |
2012年 | 168篇 |
2011年 | 141篇 |
2010年 | 97篇 |
2009年 | 93篇 |
2008年 | 126篇 |
2007年 | 125篇 |
2006年 | 102篇 |
2005年 | 102篇 |
2004年 | 97篇 |
2003年 | 77篇 |
2002年 | 76篇 |
2001年 | 14篇 |
2000年 | 9篇 |
1999年 | 9篇 |
1998年 | 20篇 |
1997年 | 22篇 |
1996年 | 18篇 |
1995年 | 19篇 |
1994年 | 19篇 |
1993年 | 16篇 |
1992年 | 13篇 |
1991年 | 10篇 |
1990年 | 10篇 |
1989年 | 5篇 |
1988年 | 7篇 |
1987年 | 3篇 |
1986年 | 6篇 |
1985年 | 1篇 |
1984年 | 2篇 |
1983年 | 2篇 |
1982年 | 2篇 |
1980年 | 2篇 |
排序方式: 共有2073条查询结果,搜索用时 15 毫秒
71.
Angiopoietin decoy secreted at tumor site impairs tumor growth and metastases by inducing local inflammation and altering neoangiogenesis 总被引:3,自引:0,他引:3
Melani C Stoppacciaro A Foroni C Felicetti F Caré A Colombo MP 《Cancer immunology, immunotherapy : CII》2004,53(7):600-608
The extracellular domain of the receptor tyrosine kinase Tie2/TEK (exTEK) has been used as an angiopoietin decoy to study the role of angiopoietins in the tumor–host interactions, using a syngeneic model of experimental metastases and subcutaneous tumor. Soluble exTEK secreted by transfected tumor cells inhibited HUVECs from forming tubes in Matrigel. ExTEK-transfected C26 colon carcinoma and TS/A mammary tumor cells displayed reduced growth rate when injected subcutaneously, and reduced ability to form experimental metastases when injected intravenously. Immunohistochemical analysis of tumors and metastases showed increased leukocytes infiltration and signs of inflammation in exTEK-secreting compared to parental tumor, as well as impairment in neo-vessel growth and organization. However, while neoangiogenesis eventually rescued in the subcutis, it failed to organize in the experimental metastases of exTEK-secreting tumor, contributing to the hampering of metastatic growth and to increased mice survival. The reactive infiltrate of C26TEK contained a different percentage of leukocytes and was responsible for the tumor inhibition. In fact, leukopenia induced by -irradiation of recipient mice or injection into interferon gamma (IFN-) gene knockout (GKO) mice resulted in reduced mouse survival and an increased number of lung metastases. On the other hand, interleukin (IL)-12 treatment prolonged the survival of mice bearing subcutaneous C26TEK but not of those bearing lung metastases, suggesting that IL-12 could exert further antiangiogenic effects at the site where the tumor can restore neoangiogenesis. These results show in vivo that reduced angiopoietin availability at the tumor site induces a local inflammatory response and impairment of neoangiogenesis which act synergistically to limit tumor growth and metastasis.Abbreviations AEC
amino-ethylcarbazole
- ELISA
enzyme-linked immunosorbent assay
- HRP
horseradish peroxidase
- HUVEC
human umbilical vascular endothelial cell
- i.v.
intravenous
- s.c.
subcutaneous
- TBS
Tris-HCl buffered solution 相似文献
72.
Marangoni A Aldini R Sambri V Giacani L Di Leo K Cevenini R 《FEMS immunology and medical microbiology》2004,40(3):187-191
Stimulation of isolated rat Kupffer cells by viable Leptospira interrogans, Treponema pallidum and Borrelia garinii elicited cellular responses resulting in the release of different tumor necrosis factor alpha (TNF-alpha) levels, depending on the spirochetes. L. interrogans induced TNF-alpha levels higher than those achieved with B. garinii and T. pallidum (in this order), but lower than the levels achieved with lipopolysaccharide (LPS). In contrast to L. interrogans, pretreatment of borreliae and treponemes with polymyxin B did not substantially diminish the ability of B. garinii and T. pallidum to stimulate Kupffer cells. Purified T. pallidum lipoproteins TpN47, TmpA, TpN15-TpN17, and B. garinii OspA induced TNF-alpha responses comparable to that achieved by LPS. This response was almost insensitive to the action of polymyxin B. 相似文献
73.
74.
Composition and mean residence time of molecular weight fractions of organic matter extracted from two soils under different forest species 总被引:2,自引:0,他引:2
Giacomo Certini Alberto Agnelli Giuseppe Corti Antonella Capperucci 《Biogeochemistry》2004,71(3):299-316
The organic matter extracted from various mineral horizons of two forest soils, one under silver fir (Abies alba Mill.), the other under European beech (Fagus sylvatica L.), was fractionated by dialysis into three fractions, 100–1000, 1000–8000, and >8000Da. On a C basis, in all horizons the recovered organic matter amounted to less than a half of the total and was mainly composed of molecules >8000Da. The 100–1000Da fraction had a principal elemental composition profoundly different from the other two fractions, which, instead differed from each other significantly only for the S content and the molar ratio of C with N. No significant difference in this regard was found between soils. The richness in O and some typical absorption bands in the FT-IR spectra indicated that the 100–1000Da fraction had a lot of carboxyl moieties. The spectroscopic (13C NMR) investigation showed that the 1000–8000 and >8000Da fractions had a prevalently aliphatic nature and signals attributable to polysaccharides (O-alkyl C) revealed overall a high presence of non-humic biopolymers. These latter were significantly more abundant, suggesting a lower degree of humification, in the >8000Da fraction than in the 1000–8000Da fraction. Comparing soils, that under beech appeared significantly richer in O-alkyl C than that under fir. The organics extracted from the A horizon of both soils had positive 14C values, indicating recent synthesis mainly due to the present forest cover. The mean residence time (MRT) of the combined 100–1000Da and 1000–8000Da fractions and the >8000Da fraction increased with depth, even to about 5000 years in the more than 1-m deep BC horizons under beech. In some cases, and especially in the soil under fir, despite higher values of 13C denoting stronger microbial decomposition, the 100–8000Da fraction showed a higher MRT than that of the >8000Da fraction, perhaps due to its ascertained lower content of non-humic biopolymers. 相似文献
75.
Manni V Lisi A Rieti S Serafino A Ledda M Giuliani L Sacco D D'Emilia E Grimaldi S 《Bioelectromagnetics》2004,25(2):118-126
This work concerns the effect of low frequency electromagnetic fields (ELF) on biochemical properties of human oral keratinocytes (HOK). Cells exposed to a 2 mT, 50 Hz, magnetic field, showed by scanning electron microscopy (SEM) modification in shape and morphology; these modifications were also associated with different actin distribution, revealed by phalloidin fluorescence analysis. Moreover, exposed cells had a smaller clonogenic capacity, and decreased cellular growth. Indirect immunofluorescence with fluorescent antibodies against involucrin and beta-catenin, both differentiation and adhesion markers, revealed an increase in involucrin and beta-catenin expression. The advance in differentiation was confirmed by a decrease of expression of epidermal growth factor (EGF) receptor in exposed cells, supporting the idea that exposure to electromagnetic field carries keratinocytes to higher differentiation level. These observations support the hypothesis that 50 Hz electromagnetic fields may modify cell morphology and interfere in differentiation and cellular adhesion of normal keratinocytes. 相似文献
76.
Di Biase A Di Benedetto R Fiorentini C Travaglione S Salvati S Attorri L Pietraforte D 《Neurochemistry international》2004,44(4):215-221
Free radicals have been implicated in the etiopathology of some neurological and demyelinating diseases. To evaluate their involvement in the cerebral form of X-linked adrenoleukodystrophy (cerALD) disorder, characterised by very long chain fatty acid (VLCFA) accumulation, we utilised an in vitro model using rat C6 glial cells, enriched in hexacosenoic acid (C26:0, HA). Modified cells were incubated in presence of oxidative stressors, such as bacterial endotoxin lipopolisaccharides (LPS) and human oxidised low-density lipoprotein (ox-LDL), and the production of proinflammatory cytokines, nitrite, nitrate and superoxide was determined in the supernatants. The results show that modified cells produce higher amounts of nitric oxide (NO) products and superoxide compared to native C6 cells, supporting the role of free radicals as important pathophysiological modulator of the neuroinflammatory response in ALD. This hypothesis suggests that the cerebral damage in ALD could be due to intracellular signalling activated by interaction of exogenous factors with the particular membrane fatty acid composition. 相似文献
77.
Cena C Boschi D Tron GC Chegaev K Lazzarato L Di Stilo A Aragno M Fruttero R Gasco A 《Bioorganic & medicinal chemistry letters》2004,14(24):5971-5974
A new class of NO-donor phenol derivatives is described. The products were obtained by joining appropriate phenols with either nitrooxy or 3-phenylsulfonylfuroxan-4-yloxy moieties. All the compounds proved to inhibit the ferrous salt/ascorbate induced lipidic peroxidation of membrane lipids of rat hepatocytes. They were also capable of dilating rat aorta strips precontracted with phenylephrine. 相似文献
78.
Magliani W Conti S Salati A Vaccari S Ravanetti L Maffei DL Polonelli L 《FEMS yeast research》2004,5(1):11-18
This review focuses on the potential of yeast killer toxin (KT)-like antibodies (KTAbs), that mimic a wide-spectrum KT through interaction with specific cell wall receptors (KTR) and their molecular derivatives (killer mimotopes), as putative new tools for transdisease anti-infective therapy. KTAbs are produced during the course of experimental and natural infections caused by KTR-bearing micro-organisms. They have been produced by idiotypic vaccination with a KT-neutralizing mAb, also in their monoclonal and recombinant formats. KTAbs and KTAbs-derived mimotopes may exert a strong therapeutic activity against mucosal and systemic infections caused by eukaryotic and prokaryotic pathogenic agents, thus representing new potential wide-spectrum antibiotics. 相似文献
79.
Cavarra E Carraro F Fineschi S Naldini A Bartalesi B Pucci A Lungarella G 《American journal of physiology. Lung cellular and molecular physiology》2004,287(6):L1186-L1192
The sensitivity to the fibrosis-inducing effect of bleomycin varies considerably from species to species, the reasons for which are unknown. The variability of the response in different strains of mice is well documented. Recent evidence indicates that the upregulated expression of cytokines and cytokine receptors may be involved. We evaluated the expression pattern of some cytokines and their receptors in C57Bl/6J bleomycin-sensitive and Balb/C bleomycin-resistant mice. Animals from both strains received, under ether anesthesia, either saline (50 microl) or bleomycin (0.1 U/50 microl) intratracheally. At various times after the treatment, the lungs were analyzed for cytokines and cytokine receptors by histochemistry and their mRNA by RNase protection assay. A significantly increased expression of TNF-alpha and IL-1beta was observed in both strains. However, an upregulated lung expression for TNF-alpha and IL-1 receptors was observed in C57Bl/6J-sensitive animals only. This profile is evident from 63 h onward. In addition to TNF-alpha, bleomycin administration also resulted in the upregulated expression of TGF-beta in the lungs of both strains at 8 h and in an enhanced expression of TGF-beta receptors I and II in C57Bl/6J mice only. The upregulation of TGF-beta receptor expression was preceded in this strain by an increased expression of IL-4, IL-13, and IL-13 receptor-alpha (at 8 h after bleomycin) and followed by an upregulation of gp130 and IL-6. The difference we observed in the cytokine receptor profile may offer an additional explanation for the different fibrogenic response of the two mouse strains to bleomycin. 相似文献
80.
Sorrentino D Faller G DeVita S Avellini C Labombarda A Ferraccioli G Kahlow-Toussaint S 《Helicobacter》2004,9(1):46-53
Background. Previous studies have shown that Helicobacter pylori seroprevalence in Sjögren's syndrome is comparable with that of the general population. However, the origin of the chronic gastropathy associated with this syndrome and the role of local autoimmunity – possibly triggered by bacterial infection – in its pathogenesis remain unclear. Materials and Methods. We initially determined the prevalence of IgG anti H. pylori in dyspeptic subjects with and without Sjögren's syndrome. In subsets of both groups we then determined anti CagA and human tissue‐tested anticanalicular/antifoveolar autoantibodies. We also compared activity, atrophy and Mucosa Associated Lymphoid Tissue (MALT) scores, as well as symptoms, before and after bacterial eradication. Results. Prevalence of H. pylori in Sjögren's syndrome patients was similar to controls: 31/54 (57%) vs. 93/150 (62%). Anti CagA prevalence was also similar in the two groups. Twenty weeks after H. pylori eradication, histological activity decreased in both groups, however, atrophy and MALT decreased significantly only in controls. Sixteen months after H. pylori eradication, 75% of Sjögren's syndrome patients still complained of dyspepsia compared with 13% of controls. Finally, antigastric autoantibodies were present in 29% of tested Sjögren's syndrome patients vs. 28% of controls. Conclusions. H. pylori infection was equally prevalent among dyspeptic Sjögren's syndrome patients and dyspeptic controls. Likewise, there were no differences regarding anti CagA prevalence or antigastric autoantibodies among the two groups. The persistence of symptoms as well as of the lymphocytic infiltration and atrophy after H. pylori eradication in Sjögren's syndrome may underlie the ‘endogenous’ and still unknown nature of the gastropathy in this condition. 相似文献