全文获取类型
收费全文 | 239篇 |
免费 | 6篇 |
出版年
2018年 | 2篇 |
2017年 | 3篇 |
2015年 | 7篇 |
2014年 | 5篇 |
2013年 | 5篇 |
2012年 | 17篇 |
2011年 | 8篇 |
2010年 | 7篇 |
2009年 | 4篇 |
2008年 | 17篇 |
2007年 | 17篇 |
2006年 | 9篇 |
2005年 | 14篇 |
2004年 | 8篇 |
2003年 | 10篇 |
2002年 | 11篇 |
2001年 | 5篇 |
2000年 | 11篇 |
1999年 | 3篇 |
1996年 | 2篇 |
1994年 | 2篇 |
1993年 | 4篇 |
1992年 | 3篇 |
1990年 | 6篇 |
1988年 | 2篇 |
1987年 | 2篇 |
1986年 | 3篇 |
1980年 | 3篇 |
1979年 | 5篇 |
1978年 | 2篇 |
1977年 | 2篇 |
1976年 | 2篇 |
1972年 | 4篇 |
1971年 | 2篇 |
1969年 | 5篇 |
1968年 | 1篇 |
1967年 | 4篇 |
1966年 | 1篇 |
1964年 | 1篇 |
1963年 | 1篇 |
1962年 | 1篇 |
1958年 | 3篇 |
1956年 | 1篇 |
1955年 | 1篇 |
1953年 | 1篇 |
1950年 | 2篇 |
1949年 | 1篇 |
1948年 | 1篇 |
1947年 | 2篇 |
1915年 | 1篇 |
排序方式: 共有245条查询结果,搜索用时 78 毫秒
21.
22.
Lehr P Billich A Wolff B Nussbaumer P 《Bioorganic & medicinal chemistry letters》2005,15(4):1235-1238
Steroid sulfatase (STS) is an attractive target for a range of oestrogen- and androgen-dependent diseases. In search of novel chemotypes of STS inhibitors, we had previously identified nortropinyl-arylsulfonylureas 1; however, while these compounds were good inhibitors of purified STS (lowest K(i)=76 nM), they showed only weak inhibition of STS activity in cells (lowest IC(50) around 2 microM). Extended structure-activity relationship studies involving modification of the phenylacetyl side chain and replacement of the nortropine element by simpler scaffolds led to the discovery of N-acyl arylsulfonamides, more specifically N-(Boc-piperidine-4-carbonyl)-benzenesulfonamides, as STS inhibitors, some of which exhibit improved cellular potency (best IC(50)=270 nM). 相似文献
23.
Cutting edge: TGF-beta signaling is required for the in vivo expansion and immunosuppressive capacity of regulatory CD4+CD25+ T cells 总被引:13,自引:0,他引:13
Huber S Schramm C Lehr HA Mann A Schmitt S Becker C Protschka M Galle PR Neurath MF Blessing M 《Journal of immunology (Baltimore, Md. : 1950)》2004,173(11):6526-6531
Data regarding the role of TGF-beta for the in vivo function of regulatory CD4(+)CD25(+) T cells (Treg) are controversial. A transgenic mouse model with impaired TGF-beta signaling specifically in T cells was used to assess the role of endogenous TGF-beta for the in vivo function of CD4(+)CD25(+) Treg in a murine model of colitis induced by dextran sulfate. Transfer of wild-type, but not transgenic CD4(+)CD25(+) Treg was found to suppress colitis in wild-type mice. In addition, by transferring CFSE-labeled CD4(+)CD25(+) Treg we could demonstrate that endogenous TGF-beta promotes the expansion of CD4(+)CD25(+) Treg in vivo. Transgenic mice themselves developed reduced numbers of peripheral CD4(+)CD25(+) Treg and were more susceptible to the induction of colitis, which could be prevented by the transfer of wild-type Treg. These data indicate that TGF-beta signaling in CD4(+)CD25(+) Treg is required for their in vivo expansion and suppressive capacity. 相似文献
24.
Antiamoebins I, III and XVI as well as several others in minor amounts were produced by four strains of the coprophilous fungus Stilbella erythrocephala (syn. S. fimetaria) in its natural substrate and in liquid culture. The total antiamoebin concentration in dung was 126-624 microg g(-1) fresh weight, with minimum inhibitory concentrations against most other coprophilous fungi being at or below 100 microg mL(-1). Myrocin B, not previously described from S. erythrocephala, was also produced, but only at low, nonfungicidal levels (< 5.3 microg g(-1)). No other antifungal substances were detected. It is concluded that antiamoebins are responsible for antibiosis in dung colonized by S. erythrocephala. 相似文献
25.
Reconstructed human epidermis for skin absorption testing: results of the German prevalidation study
Schäfer-Korting M Bock U Gamer A Haberland A Haltner-Ukomadu E Kaca M Kamp H Kietzmann M Korting HC Krächter HU Lehr CM Liebsch M Mehling A Netzlaff F Niedorf F Rübbelke MK Schäfer U Schmidt E Schreiber S Schröder KR Spielmann H Vuia A 《Alternatives to laboratory animals : ATLA》2006,34(3):283-294
Exposure to chemicals absorbed by the skin can threaten human health. In order to standardise the predictive testing of percutaneous absorption for regulatory purposes, the OECD adopted guideline 428, which describes methods for assessing absorption by using human and animal skin. In this study, a protocol based on the OECD principles was developed and prevalidated by using reconstructed human epidermis (RHE). The permeation of the OECD standard compounds, caffeine and testosterone, through commercially available RHE models was compared to that of human epidermis and animal skin. In comparison to human epidermis, the permeation of the chemicals was overestimated when using RHE. The following ranking of the permeation coefficients for testosterone was obtained: SkinEthic > EpiDerm, EPISKIN > human epidermis, bovine udder skin, pig skin. The ranking for caffeine was: SkinEthic, EPISKIN > bovine udder skin, EpiDerm, pig skin, human epidermis. The inter-laboratory and intra-laboratory reproducibility was good. Long and variable lag times, which are a matter of concern when using human and pig skin, did not occur with RHE. Due to the successful transfer of the protocol, it is now in the validation process. 相似文献
26.
27.
28.
Root inoculation with a forest soil streptomycete leads to locally and systemically increased resistance against phytopathogens in Norway spruce 总被引:2,自引:0,他引:2
Soil streptomycetes are commonly antagonistic against plant pathogens. However, interactions involving increased defense responses in the host plant, leading to suppression of plant disease development, have not yet been detailed. Here, the mechanisms were studied of disease suppression by Streptomyces sp. GB 4-2 against Heterobasidion root and butt rot in Norway spruce (Picea abies) seedlings. GB 4-2 promoted mycelial growth of the phytopathogenic fungus, germination rate of fungal spores, extension of germ tubes and early colonization of outer cortical layers of the plant root. Reduced colonization of the inner cortical cell layers was accompanied by the induction of cell wall appositions, and increased xylem formation in the vascular cylinder emerged after bacterium-fungus coinoculation. Bacterial treatment led to decreased water content in roots and needles and increased photosynthetic yield (F(v)/F(m)) and peroxidase activities in needles. The infection of needles by Botrytis cinerea was reduced by bacterial pretreatment. Complex interactions of GB 4-2 with Norway spruce and Heterobasidion abietinum were discovered. The bacterium promoted the growth of the phytopathogenic fungus but induced plant defense responses. Host responses indicate that GB 4-2 induces both local and systemic defense responses in Norway spruce. 相似文献
29.
Expression of uncoupling protein-3 in subsarcolemmal and intermyofibrillar mitochondria of various mouse muscle types and its modulation by fasting. 总被引:10,自引:0,他引:10
Maria Jimenez Cedric Yvon Lorenz Lehr Bertrand Léger Patrick Keller Aaron Russell Fran?oise Kuhne Pierre Flandin Jean-Paul Giacobino Patrick Muzzin 《European journal of biochemistry》2002,269(12):2878-2884
Uncoupling protein-3 (UCP3) is a mitochondrial inner-membrane protein abundantly expressed in rodent and human skeletal muscle which may be involved in energy dissipation. Many studies have been performed on the metabolic regulation of UCP3 mRNA level, but little is known about UCP3 expression at the protein level. Two populations of mitochondria have been described in skeletal muscle, subsarcolemmal (SS) and intermyofibrillar (IMF), which differ in their intracellular localization and possibly also their metabolic role. To examine if UCP3 is differentially expressed in these two populations and in different mouse muscle types, we developed a new protocol for isolation of SS and IMF mitochondria and carefully validated a new UCP3 antibody. The data show that the density of UCP3 is higher in the mitochondria of glycolytic muscles (tibialis anterior and gastrocnemius) than in those of oxidative muscle (soleus). They also show that SS mitochondria contain more UCP3 per mg of protein than IMF mitochondria. Taken together, these results suggest that oxidative muscle and the mitochondria most closely associated with myofibrils are most efficient at producing ATP. We then determined the effect of a 24-h fast, which greatly increases UCP3 mRNA (16.4-fold) in muscle, on UCP3 protein expression in gastrocnemius mitochondria. We found that fasting moderately increases (1.5-fold) or does not change UCP3 protein in gastrocnemius SS or IMF mitochondria, respectively. These results show that modulation of UCP3 expression at the mRNA level does not necessarily result in similar changes at the protein level and indicate that UCP3 density in SS and IMF mitochondria can be differently affected by metabolic changes. 相似文献
30.
Afshin Ghasemi Alwine Schulze Elfringhoff Matthias Lehr 《Journal of enzyme inhibition and medicinal chemistry》2013,28(5):429-437
Recently we found that 1-methyldodecanoylindole-2-carboxylic acid (1) and 1-[2-(4-carboxyphenoxy)ethyl]-3-dodecanoylindole-2-carboxylic acid (4) were inhibitors of the cytosolic phospholipase A2α (cPLA2α)-mediated arachidonic acid release in calcium ionophore A23187-stimulated human platelets with IC50-values of 4.8 μM (1) and 0.86 μM (4). We have now replaced the 3-acyl residue of these compounds by alkylated sulfinyl-, sulfony-, sulfinamoyl-, sulfamoyl-, carbonylamino-, or carbonylaminomethyl-substituents. Structure–activity relationship studies revealed that the pronounced cellular activity of 4 strongly depends on the presence of the 3-acyl moiety. Surprisingly, when testing 4 and its derivatives in an assay with the isolated cPLA2, none of these compounds showed an inhibitory potency at 10 μM indicating that they do not inhibit cPLA2α in the cells by a direct interaction with the active site of the enzyme. 相似文献