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排序方式: 共有279条查询结果,搜索用时 15 毫秒
31.
Tully DC Liu H Alper PB Chatterjee AK Epple R Roberts MJ Williams JA Nguyen KT Woodmansee DH Tumanut C Li J Spraggon G Chang J Tuntland T Harris JL Karanewsky DS 《Bioorganic & medicinal chemistry letters》2006,16(7):1975-1980
A series of N(alpha)-2-benzoxazolyl-alpha-amino acid-(arylaminoethyl)amides were identified as potent, selective, and noncovalent inhibitors of cathepsin S. Structure-activity relationships including strategies for modulating the selectivities among cathepsins S, K, and L, and in vivo pharmacokinetics are discussed. A X-ray structure of compound 3 bound to the active site of cathepsin S is also reported. 相似文献
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Claus Sternberg Bjarke B. Christensen Tove Johansen Alex Toftgaard Nielsen Jens Bo Andersen Michael Givskov Sren Molin 《Applied microbiology》1999,65(9):4108-4117
In microbial communities such as those found in biofilms, individual organisms most often display heterogeneous behavior with respect to their metabolic activity, growth status, gene expression pattern, etc. In that context, a novel reporter system for monitoring of cellular growth activity has been designed. It comprises a transposon cassette carrying fusions between the growth rate-regulated Escherichia coli rrnBP1 promoter and different variant gfp genes. It is shown that the P1 promoter is regulated in the same way in E. coli and Pseudomonas putida, making it useful for monitoring of growth activity in organisms outside the group of enteric bacteria. Construction of fusions to genes encoding unstable Gfp proteins opened up the possibility of the monitoring of rates of rRNA synthesis and, in this way, allowing on-line determination of the distribution of growth activity in a complex community. With the use of these reporter tools, it is demonstrated that individual cells of a toluene-degrading P. putida strain growing in a benzyl alcohol-supplemented biofilm have different levels of growth activity which develop as the biofilm gets older. Cells that eventually grow very slowly or not at all may be stimulated to restart growth if provided with a more easily metabolizable carbon source. Thus, the dynamics of biofilm growth activity has been tracked to the level of individual cells, cell clusters, and microcolonies. 相似文献
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Sverrisdóttir YB Mogren T Kataoka J Janson PO Stener-Victorin E 《American journal of physiology. Endocrinology and metabolism》2008,294(3):E576-E581
Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disturbance among women of reproductive age and is proposed to be linked with size at birth and increased prevalence of cardiovascular disease. A disturbance in the sympathetic nervous system may contribute to the etiology of PCOS. This study evaluates sympathetic outflow in PCOS and its relation to size at birth. Directly recorded sympathetic nerve activity to the muscle vascular bed (MSNA) was obtained in 20 women with PCOS and in 18 matched controls. Ovarian ultrasonographic evaluation, biometric, hormonal, and biochemical parameters were measured, and birth data were collected. Women with PCOS had increased MSNA (30 +/- 8 vs. 20 +/- 7 burst frequency, P < 0.0005) compared with controls. MSNA was positively related to testosterone (r = 0.63, P < 0.005) and cholesterol (r = 0.55, P = 0.01) levels in PCOS, which, in turn, were not related to each other. Testosterone level was a stronger predictor of MSNA than cholesterol. Birth size did not differ between the study groups. This is the first study to directly address sympathetic nerve activity in women with PCOS and shows that PCOS is associated with high MSNA. Testosterone and cholesterol levels are identified as independent predictors of MSNA in PCOS, although testosterone has a stronger impact. The increased MSNA in PCOS may contribute to the increased cardiovascular risk and etiology of the condition. In this study, PCOS was not related to size at birth. 相似文献
37.
Torben Clausen Tove Lindahl Andersen Marianne Stürup-Johansen Olga Petkova 《生物化学与生物物理学报:生物膜》1981,646(2):261-267
(1) The effects of vanadate of hexose transport, 45Ca-exchange and (Na+, K+)-contents have been characterized in isolated adipose tissue and skeletal muscles of the rat. (2) In whole epididymal fat pads, vanadate (0.5–5.0 mM) markedly stimulated the uptake of 2-deoxyl[14C]glucose as well as the efflux of . (3) Within the same concentration range, vanadate induced an early increase in 45Ca-washout from preloaded fat pads. The maximum increases in the fractional losses of and 45Ca were significantly correlated (, ). (4) In extensor digitorum longus and soleus muscles, vanadate (0.5–5.0 mM) stimulated the efflux of and this effect was preceded by a rise in the washout of 45Ca. The maximum increases in the fractional losses of and 45Ca were significantly correlated (, ). (5) In extensor digitorum longus and soleus muscles, vanadate increased K+-contents and decreased Na+ contents. (6) The stimulation of 45Ca-washout presumably reflects an increase in the cytoplasmic Ca2+ level, brought about by an inhibitory effect of vanadate on the Ca2+-sensitive ATPase of the sarcoplasmic or the endoplasmic reticulum. As demonstrated for most other insulin-like agents (Sørensen, S.S., Christensen, F. and Clausen, T. (1980) Biochim. Biophys. Acta 602, 433–445), the stimulating effect of vanadate on glucose transport appears to be associated with or mediated by a rise in the cytoplasmic Ca2+ level. 相似文献
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Tove Olafsen Charlotte K. Munthe Lund Øyvind S. Bruland Inger Sandlie Terje E. Michaelsen 《Cancer immunology, immunotherapy : CII》1999,48(7):411-418
Osteosarcoma is the commonest malignant tumour of the bones. The presence of micrometastases at the time of primary diagnosis
is associated with poor prognosis. Despite developments in surgery and aggressive chemotherapy, about 50% of the patients
still succumb to the disease. Thus, there is a need to develop alternative treatment modalities. One such strategy is to use
antibodies with improved effector functions. The two monoclonal antibodies, TP-1 and TP-3, recognize a tumour-associated antigen
on human osteosarcoma cells. In the present study, we describe the cloning of the TP-1 variable genes, and the production
of complete chimeric mouse/human monoclonal antibodies. Constructs containing the constant genes from human IgG1, IgG3 or
a mutant IgG3 with a shortened hinge region, called m15, were expressed in the mouse myeloma cell line, NS0. The m15 mutant
has been shown to be very potent in triggering complement-mediated lysis. Our goal was to investigate whether this mutant
could overcome the complement protection on human osteosarcoma cells, which is generally present on all human cells. We found
that the target cells expressed several membrane-bound complement inhibitors, and that masking of these inhibitors rendered
the cells sensitive to lysis. The m15 mutant exhibited greater lytic activity than both IgG3 and IgG1, although it could not
cause extensive killing of the target cells alone.
Received: 21 January 1999 / Accepted: 3 June 1999 相似文献
40.
Engineering bispecificity into a single albumin-binding domain 总被引:2,自引:0,他引:2
Bispecific antibodies as well as non-immunoglobulin based bispecific affinity proteins are considered to have a very high potential in future biotherapeutic applications. In this study, we report on a novel approach for generation of extremely small bispecific proteins comprised of only a single structural domain. Binding to tumor necrosis factor-α (TNF-α) was engineered into an albumin-binding domain while still retaining the original affinity for albumin, resulting in a bispecific protein composed of merely 46 amino acids. By diversification of the non albumin-binding side of the three-helix bundle domain, followed by display of the resulting library on phage particles, bispecific single-domain proteins were isolated using selections with TNF-α as target. Moreover, based on the obtained sequences from the phage selection, a second-generation library was designed in order to further increase the affinity of the bispecific candidates. Staphylococcal surface display was employed for the affinity maturation, enabling efficient isolation of improved binders as well as multiparameter-based sortings with both TNF-α and albumin as targets in the same selection cycle. Isolated variants were sequenced and the binding to albumin and TNF-α was analyzed. This analysis revealed an affinity for TNF-α below 5 nM for the strongest binders. From the multiparameter sorting that simultaneously targeted TNF-α and albumin, several bispecific candidates were isolated with high affinity to both antigens, suggesting that cell display in combination with fluorescence activated cell sorting is a suitable technology for engineering of bispecificity. To our knowledge, the new binders represent the smallest engineered bispecific proteins reported so far. Possibilities and challenges as well as potential future applications of this novel strategy are discussed. 相似文献