全文获取类型
收费全文 | 1535篇 |
免费 | 130篇 |
国内免费 | 29篇 |
出版年
2024年 | 2篇 |
2023年 | 22篇 |
2022年 | 30篇 |
2021年 | 45篇 |
2020年 | 38篇 |
2019年 | 45篇 |
2018年 | 47篇 |
2017年 | 36篇 |
2016年 | 54篇 |
2015年 | 53篇 |
2014年 | 86篇 |
2013年 | 71篇 |
2012年 | 48篇 |
2011年 | 103篇 |
2010年 | 41篇 |
2009年 | 79篇 |
2008年 | 74篇 |
2007年 | 82篇 |
2006年 | 61篇 |
2005年 | 74篇 |
2004年 | 77篇 |
2003年 | 51篇 |
2002年 | 47篇 |
2001年 | 25篇 |
2000年 | 33篇 |
1999年 | 42篇 |
1998年 | 34篇 |
1997年 | 33篇 |
1996年 | 46篇 |
1995年 | 37篇 |
1994年 | 40篇 |
1993年 | 29篇 |
1992年 | 28篇 |
1991年 | 17篇 |
1990年 | 5篇 |
1989年 | 4篇 |
1988年 | 2篇 |
1987年 | 6篇 |
1985年 | 6篇 |
1984年 | 11篇 |
1983年 | 4篇 |
1982年 | 5篇 |
1981年 | 3篇 |
1980年 | 4篇 |
1979年 | 7篇 |
1976年 | 1篇 |
1975年 | 1篇 |
1974年 | 1篇 |
1973年 | 1篇 |
1972年 | 1篇 |
排序方式: 共有1694条查询结果,搜索用时 13 毫秒
1.
2.
Rashi Verma Monika Yadav Rajabrata Bhuyan Shweta Aggarwal Arnab Nayek 《Journal of receptor and signal transduction research》2016,36(6):601-616
Computer-aided antibody engineering has been successful in the design of new biologics for disease diagnosis and therapeutic interventions. Interleukin-6 (IL-6), a well-recognized drug target for various autoimmune and inflammatory diseases such as rheumatoid arthritis, multiple sclerosis, and psoriasis, was investigated in silico to design potential lead antibodies. Here, crystal structure of IL-6 along with monoclonal antibody olokizumab was explored to predict antigen–antibody (Ag???Ab)-interacting residues using DiscoTope, Paratome, and PyMOL. Tyr56, Tyr103 in heavy chain and Gly30, Ile31 in light chain of olokizumab were mutated with residues Ser, Thr, Tyr, Trp, and Phe. A set of 899 mutant macromolecules were designed, and binding affinity of these macromolecules to IL-6 was evaluated through Ag???Ab docking (ZDOCK, ClusPro, and Rosetta server), binding free-energy calculations using Molecular Mechanics/Poisson Boltzman Surface Area (MM/PBSA) method, and interaction energy estimation. In comparison to olokizumab, eight newly designed theoretical antibodies demonstrated better result in all assessments. Therefore, these newly designed macromolecules were proposed as potential lead antibodies to serve as a therapeutics option for IL-6-mediated diseases. 相似文献
3.
CHRISTOPHE GONINDARD CATHERINE GOIGOUX ETIENNE HOLLANDE LUCIEN DUSSOURD D'HINTERLAND 《Pigment cell & melanoma research》1996,9(3):148-153
The injection of α-MSH or of one of its analogues ([Nle4-D.Phe7] α-MSH4–10) reduced, in vivo, the release of two cytokines (IL-1α and TNFα) involved in inflammation. The inflammatory state was induced in BALB/c mice by intraperitoneal injection of a sublethal dose of lipopolysaccharides (LPS). The assay of these cytokines by ELISA showed a reduction of 20% with α-MSH and between 30 and 60% with the α-MSH analogue. The α-MSH or the analogue was administered in one of two ways: intravenously or subcutaneously. The most efficient method seemed to be the subcutaneous one because it improved the activity 10,000 times more than the intravenous method. Moreover, the analogue induced a regression of mortality in the animals treated by the intravenous method. Our results show that α-MSH and one of its analogues inhibit IL-1α and TNFα, and can be used as anti-inflammatory molecules. 相似文献
4.
The extent of vertical migration of 33 P in thalli of the heathland lichen Cladonia portentosa was investigated under field conditions. 33 P-labelled orthophosphate was introduced into the bottom 25 mm of podetia cut to a length of 50 mm from the apices. The distribution of label was scanned using a molecular imager immediately after incubation, and after growing for 8 wk and 6 months. Differences in the relative distribution of label between podetia harvested at the beginning and the end of the experiment showed that there had been a significant migration of 33 P upwards out of the labelled 25 mm stratum towards the apex. This was confirmed by statistically significant changes in the median (md) and the 90 percentile of total relative distribution of 33 P label. In a control treatment in which label was introduced into the apical 25 mm of podetia, which were then grown inverted (top down), no upward movement of label was detected. By contrast, a statistically significant reduction in the md of the distribution indicated migration downwards towards the thallus apex. The results are consistent with the hypothesis that P is recycled within podetia of mat-forming lichens, migrating from degrading basal regions upwards to the growing apices following a source–sink relationship. 相似文献
5.
A. Tyagi J. Hermans J. Steppuhn Ch. Jansson F. Vater R. G. Herrmann 《Molecular & general genetics : MGG》1987,207(2-3):288-293
Summary Several cDNA clones encoding the 33 kDa protein associated with the photosynthetic water oxidation activity of spinach were sequenced. A 1208 bp insert of one of the clones encodes the entire 331 amino acid residues of the precursor protein including 84 amino acids (8.5 kDa) of the amino-terminal transit peptide, 49 bp of the 5 and 111 bp of the 3 untranslated segment of the mRNA. The 3 poly(A) tail starts 19 bp downstream from a putative polyadenylation signal, TATAAA. The hydrophilic mature protein consists of 247 amino acid residues corresponding to an Mr of 26.5 kDa, which is 6.5 kDa smaller than the value determined by SDS-polyacrylamide gel electrophoresis (33–34 kDa), and shows a certain degree of conservation with the putative Mn-complexing active sites of bacterial Mn-dependent superoxide dismutases. The anatomy of the unusually long transit sequence is discussed with regard to current concepts of protein import into and protein routein within the organelle. 相似文献
6.
7.
Howard R. Hubbell George D. Gibson Robert D. Bigler 《Cancer immunology, immunotherapy : CII》1992,34(4):259-264
Summary Lymphokine-activated killer (LAK) cell activity was measured in human peripheral blood mononuclear cells (PBMC) treated in vitro for 3 days with recombinant interleukin-2 (rIL-2) and mismatched double-stranded RNA (dsRNA). Lytic activity was measured utilizing K562 (NK-sensitive) and 786-0 (NK-resistant) target cells. PBMC cultured with rIL-2 (10–1000 BRMP U/ml) alone showed concentration-dependent lytic activity against the 786-0 target cells, while cells cultured in unsupplemented medium or medium supplemented with mismatched dsRNA (200 µg/ml) alone could not lyse the 786-0 targets. The combination of mismatched dsRNA with suboptimal concentrations of rIL-2 (10–30 U/ml) showed enhancement of both natural killer (NK) and LAK cell activities. The uptake of [3H]thymidine by treated effector cells was dependent on time and rIL-2 concentration and was not increased in the cells treated with low-dose rIL-2/mismatched dsRNA, compared to those treated with low-dose rIL-2 or mismatched dsRNA alone. Similarly, changes in the expression of CD3, CD4, CD8, CD57, CD16 and CD25 cell surface antigens were dependent on rIL-2 concentration and not altered by the presence of mismatched dsRNA. These results indicate that mismatched dsRNA can potentiate rIL-2-induced LAK cell activity by increasing the functional activity per cell, rather than by increasing the number of activated cells. 相似文献
8.
Shinichi Ikemoto Seiji Wada Masato Kamizuru Nobuyuki Hayahara Taketoshi Kishimoto Masanobu Maekawa 《Cancer immunology, immunotherapy : CII》1992,34(5):289-293
Summary The authors examined interleukin-2 (IL-2) production and interferon (IFN) production of peripheral blood mononuclear cells in 28 patients with renal cell carcinoma and 17 control subjects. The peripheral blood was obtained prior to the initiation of therapeutic procedures. The patients were divided into two groups according to tumor size, 5 cm and >5 cm. The production of IL-2 and IFN was measured by immunoradiometric assay. As a result, in the patients with tumors >5 cm, IL-2 and IFN production was impaired. However, in the patients with tumors 5 cm, IFN production was enhanced, though IL-2 production was not significantly different from that of the control subjects. There was no significant correlation between IL-2 production and IFN production. 相似文献
9.
The interaction between interleukin IL-1α and PGE2 on P388D2 on cells has been investigated. Preincubation of murine macrophage-like cells, P388D1, with IL-1α (0–73 pM) reduced the binding of PGE2 to these cells in a concentration-dependent manner. Scatchard analysis showed that IL-1α decreased the PGE2 binding by lowering both the high and low affinity receptor binding capacities (from 0.31 ± 0.02 to 0.12 ± 0.01 fmol/106 cells for the high affinity receptor binding sites and from 2.41 ± 0.12 to 1.51 ± 0.21 fmol/106 cells for the low affinity receptor binding sites). However, the dissociation constants of the receptor of the IL-1α-treated cells remained unchanged. Inhibition of PGE2 binding IL-1α did not involve changes in either protein phosphorylation or intracellular cyclic AMP levels. Our data clearly show that IL-1α inhibits the binding of PGE2 to monocytes/macrophages and may thereby counter the immunosuppressive actions of PGE2. 相似文献
10.
Stephen G. Swisher Timothy M. Anderson Duan-Ren Wen Mark A. Stene Alistair J. Cochran Sidney H. Golub E. Carmack Holmes 《Cancer immunology, immunotherapy : CII》1991,33(5):327-332
Summary We administered preoperative low-dose interleukin-2 (IL-2) to 10 patients undergoing thoracotomy for pulmonary tumors. The in vivo effect of IL-2 on tumor-associated lymphocyte activity was assessed in the resected specimens by immunohistochemistry and compared with observations in 45 patients who did not receive IL-2. H & E evaluation revealed an increase in intra- and peritumoral lymphocyte infiltration in the IL-2-treated patients. Immunopathological evaluation with monoclonal antibodies revealed that this lymphocyte infiltration was predominantly CD5-positive T cells. The amount of intra-and peritumoral lymphocyte activity correlated with the dose of IL-2 administered (6000–90 000 international units/kg every 8 h for 48 h. IL-2-treated patients showed increases in T-cell-associated activation markers (IL-2 -receptor, transferrin receptor and HLA-DR) on peritumoral lymphocytes, but not on intratumoral lymphocytes. We previously reported that low-dose IL-2 increases the intrinsic natural killer cell cytotoxicity of intratumoral lymphocytes and suggest that this lymphocyte infiltration is further evidence that low-dose IL-2 can augment in vivo lymphocyte activity at the tumor site.This work was supported in part by USPHS grants CA 44 352 (S. H. G.) and 43 658 (A. J. C.). S. G. S. was supported by NIH Surgical Oncology Training Grant CA 09 010 相似文献