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111.
《Cytokine》2016
OX40 receptor-expressing regulatory T cells (Tregs) populate tumors and suppress a variety of immune cells, posing a major obstacle for cancer immunotherapy. Different ways to functionally inactivate Tregs by triggering OX40 receptor have been suggested, including anti-OX40 antibodies and Fc:OX40L fusion proteins. To investigate whether the soluble extracellular domain of OX40L (OX40Lexo) is sufficient to enhance antitumor immune response, we generated an OX40Lexo-expressing CT26 colon carcinoma cell line and studied its tumorigenicity in immunocompetent BALB/c and T cell deficient nu/nu mice.We found that soluble OX40L expressed in CT26 colon carcinoma favors the induction of an antitumor response which is not limited just to cells co-expressing EGFP as an antigenic determinant, but also eliminates CT26 cells expressing another fluorescent protein, KillerRed. Tumor rejection required the presence of T lymphocytes, as indicated by the unhampered tumor growth in nu/nu mice. Subsequent re-challenge of tumor-free BALB/c mice with CT26 EGFP cells resulted in no tumor growth, which is indicative of the formation of immunological memory. Adoptive transfer of splenocytes from mice that successfully rejected CT26 OX40Lexo EGFP tumors to naïve mice conferred 100% resistance to subsequent challenge with the CT26 EGFP tumor. 相似文献
112.
Paul L. Black Hamblin Phillips Henry R. Tribble Robin Pennington Mark schneider James E. Talmadge 《Cancer immunology, immunotherapy : CII》1993,37(5):299-306
The mechanism of therapeutic activity for recombinant murine interferon-(rMu IFN) in the treatment of metastatic disease was investigated by comparing effector cell augmentation with therapeutic activity in mice bearing experimental lung metastases (B16-BL6 melanoma). Effector cell functions in spleen, peripheral blood, and lung (the tumor-bearing organ) were tested after 1 week and 3 weeks of rMu IFN administration (i.v. three times per week). Natural killer (NK), lymphokine-activated killer (LAK), cytolytic T lymphocyte (CTL) activities against specific and nonspecific targets, and macrophage tumoristatic activity were measured. rMu IFN demonstrated immunomodulatory activity in most assays of immune function. The optimal therapeutic protocol of rMu IFN (2.5×106 U/kg, three times per week) prolonged survival and decreased the number of pulmonary metastatic foci. This therapeutic activity was correlated with specific CTL activity from pulmonary parenchymal mononuclear cells (PPMC), but not from spleen or blood. Macrophage tumoristatic activity in PPMC also correlated with therapeutic activity, but activity in alveolar macrophages did not. However, therapeutic activity did not correlate with NK or LAK activity at any site. These results demonstrate that the optimal therapeutic protocol is the same as the optimal immunomodulatory dose for pulmonary CTL and macrophage activities. Furthermore, while immunological monitoring may help to optimize treatment protocols, current monitoring procedures that use readily accessible sites, particularly peripheral blood, may not accurately predict the therapeutic efficacy of biological response modifiers in clinical trials.By acceptance of this article, the publisher or recipient acknowledges the right of the US. Government to retain a nonexclusive, royalty-free license in and to any copyright covering the articleThis research was sponsored by the DHHS, under contract N01-23910 with Program Resources Inc. The contents of this publication do not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government 相似文献
113.
Valery Kudryashov Hyunjin M. Kim Govindaswami Ragupathi Samuel J. Danishefsky Philip O. Livingston K. O. Lloyd 《Cancer immunology, immunotherapy : CII》1998,45(6):281-286
Many human carcinomas overexpress the Lewisy (Ley) blood-group epitope [Fucα1→2Galβ1→4 (Fucα1→3)GlcNAcβ1→3Gal-]. With a view to developing Ley based vaccines we have examined the immunogenicity of Ley-protein conjugates in mice. Ley pentasaccharide was synthesized as its allyl glycoside and coupled to keyhole limpet hemocyanin (KLH) by reductive amination
or by a novel method utilizing a maleido-derivitized alkyl carboxyhydrazide as a bridging group to 2-iminothiolane-derivitized
KLH. Ley oligosaccharide was also coupled to bovine serum albumin by reductive amination. Immunization of groups of mice with the
three conjugates, together with the immunological adjuvant QS21, showed that Ley oligosaccharide directly coupled to KLH was the most efficient conjugate for eliciting IgG and IgM antibody responses to
naturally occurring forms of Ley epitopes carried on mucins and glycolipids. These antibodies were also reactive with and cytotoxic to a human breast cancer
cell line expressing Ley (MCF-7). These experiments suggest that Ley-KLH antigen and QS21 adjuvant could be considered as an immunogenic therapeutic vaccine in carcinoma patients.
Received: 28 March 1997 / Accepted: 2 September 1997 相似文献
114.
Carlos M.G. Azevedo Carlos M.M. Afonso Diana Sousa Raquel T. Lima M. Helena Vasconcelos Madalena Pedro João Barbosa Arlene G. Corrêa Salette Reis Madalena M.M. Pinto 《Bioorganic & medicinal chemistry》2013,21(11):2941-2959
A promising antitumor xanthone derivative was optimized following a multidimensional approach that involved the synthesis of 17 analogues, the study of their lipophilicity and solubility, and the evaluation of their growth inhibitory activity on four human tumor cell lines. A new synthetic route for the hit xanthone derivative was also developed and applied for the synthesis of its analogues. Among the used cell lines, the HL-60 showed to be in general more sensitive to the compounds tested, with the most potent compound having a GI50 of 5.1 μM, lower than the hit compound. Lipophilicity was evaluated by the partition coefficient (Kp) of a solute between buffer and two membrane models, namely liposomes and micelles. The compounds showed a log Kp between 3 and 5 and the two membrane models showed a good correlation (r2 = 0.916) between each other. Studies concerning relationship between solubility and structure were developed for the hit compound and 5 of its analogues. 相似文献
115.
Nakanishi J Wada Y Matsumoto K Azuma M Kikuchi K Ueda S 《Cancer immunology, immunotherapy : CII》2007,56(8):1173-1182
PURPOSE: The programmed death-1 (PD-1)/B7-H1 (also called PD-L1) pathway negatively regulates T cell activation and has been suggested to play an important role in regulating antitumor host immunity. To investigate the clinical significance of B7-H1 expression to the tumor grade and postoperative prognosis of patients with urothelial cancer, we analyzed the relationship between B7-H1 expression and various clinicopathological features and postoperative prognosis. EXPERIMENTAL DESIGN: Sixty-five urothelial cancer cases were examined. B7-H1 expression in tumors and the numbers and phenotypes of tumor-infiltrating lymphocytes were evaluated by immunohistochemistry and flow cytometry. RESULTS: A substantial expression of B7-H1 was observed in all urothelial cancers investigated. Tumor specimens from patients with higher WHO grade or primary tumor classifications showed significantly higher percentages of tumor-associated B7-H1. Tumor-associated B7-H1 expression was significantly associated with a high frequency of postoperative recurrence and poor survival rate. Furthermore, multivariate analysis indicated that tumor-associated B7-H1 was more significant prognostic factor than WHO grade. CONCLUSIONS: Our results demonstrate that the aberrant expression of B7-H1 in urothelial cancer is associated with aggressive tumors, suggesting a regulatory role of tumor-associated B7-H1 in antitumor immunity. Therefore, the manipulation of tumor-associated B7-H1 may become a beneficial target for immunotherapy in human urothelial cancer. 相似文献
116.
Jin Zhao Jianteng Wei Ming Liu Lin Xiao Ning Wu Ge Liu Haijuan Huang Yuyan Zhang Lanhong Zheng Xiukun Lin 《Biochimie》2013
Previous study in our laboratory confirmed that a novel polypeptide, CS5931 derived from Ciona savignyi possesses potent antitumor activity. In the present study, the full length cDNA of CS5931 precursor, termed Cs-pgrn-1 was cloned. The complete cDNA sequence of this gene consists of 685 bp containing an open reading frame (ORF) of 522 bp (173 amino acid residues). In silico analysis revealed that the polypeptide consists of two identical domains, similar with granulin (GRN) found in other species, and each of the domain encodes a polypeptide identical with CS5931. Phylogenetic analysis confirmed that CS5931 shares high homology with Ciona intestinalis GRN and is conserved during evolution. The polypeptide also shows high similarity with human GRN A, B, and C. Prediction of 3D protein structure revealed the 3D structure of CS5931 is very similar with human GRN A. The CS5931 was expressed using a prokaryotic expression system and the purified polypeptide inhibited the growth of several tumor cell lines in vitro via apoptotic pathway. Our study revealed that CS5931 has the potential to be developed as a novel antitumor agent. 相似文献
117.
In the present work, we measured survival and the platinum on the genome after treatment of repair-proficient or repair-deficient Escherichia coli strains with trans-[PtCl2(E-iminoether)2] and compared these results with the effects of “classical” cisplatin. We found that toxicity of antitumor trans-[PtCl2(E-iminoether)2] in repair-deficient trains was much less than that of cisplatin. This markedly reduced toxicity was not a consequence of the reduced uptake or low levels of DNA binding in the bacteria cells but rather appeared to reflect DNA binding mode of this trans-platinum drug different from that of cisplatin. 相似文献
118.
《Bioorganic & medicinal chemistry letters》2020,30(9):127067
Adenosine pathway, including its generating enzyme (CD73) and its receptors represents a key target for cancer immunotherapy. Here we aimed to search for novel compounds able to co-target the CD73 and the A2A adenosine receptor (A2A AR) as dual-blockers of adenosine generation and activity. The design project was to combine in the same molecule the thiazolo[5,4-d]pyrimidine core, an essential pharmacophoric feature to block the A2A AR, with a benzenesulfonamide group which is a characteristic group of CD73 inhibitors. Most of the reported compounds resulted in inverse agonists of the human (h) A2A AR endowed with high affinity, selectivity and potency. However they were weak inhibitors of CD73 enzyme. Nevertheless, this study can be considered as a starting point to develop more active compounds. 相似文献
119.
Wei Guo Zhenyuan Miao Chunquan Sheng Jianzhong Yao Wenfeng Liu Lingjian Zhu Yongqiang Zhang Pengfei Cheng Guoqiang Dong Chunlin Zhuang Wannian Zhang 《化学与生物多样性》2011,8(7):1266-1273
Six 9‐(heteroarylmethylidene)amino derivatives, 2a – 2f , of homocamptothecin were synthesized for the first time by total synthesis in 22 steps and biologically evaluated as inhibitors of topoisomerase I. Moreover, the antitumor activities of 2a – 2f against three human tumor cell lines, i.e., A‐549, MDA‐MB‐435, and HCT‐116, were determined and the results showed that compound 2c was the most active homocamptothecin derivative against the A‐549 (IC50=0.046 μM ) and HTC‐116 tumor cells (IC50=3.67 μM ), with a ca. 50 times higher activity than the reference drug topotecan (TPT) against the lung cancer cell line A‐549. 相似文献
120.
Kamalakannan Palanichamy 《Inorganica chimica acta》2006,359(1):44-52
This work reports the synthesis, characterization, and aqueous chemistry of a series of cytotoxic [Au(polypyridyl)Cl2]PF6 complexes {(where polypyridyl = dipyrido[3,2-f:2′,3′-h] quinoxaline (DPQ), dipyrido[3,2-a:2′,3′-c] phenazine (DPPZ) and dipyrido[3,2-a:2′,3′-c](6,7,8,9-tetrahydro) phenazine (DPQC))}. The crystal structure of [Au(DPQ)Cl2]PF6 was determined as example of the series and exhibits the anticipated square planar geometry common for d8 coordination complexes. The crystals of the complex belong to the space group P21/n with a = 7.624(2) Å, b = 18.274(5) Å, c = 14.411(14) Å, β = 98.03(3)°, and Z = 4. In 1H NMR studies of these compounds in the presence of aqueous buffer, all four complexes rapidly converted to the dihydroxy species [Au(polypyridyl)(OH)2] in a stepwise fashion. However, the [Au(polypyridyl)]3+ fragment believed to impart cytotoxicity in human ovarian cancer cell lines (A2780) remained intact and appeared stable for days. It was also noted that these Au(III) complexes were readily reduced in the presence of the common biological reducing agents, reduced glutathione and sodium ascorbate. How solution and redox stability may affect the biological activity of these novel Au(III) complexes is discussed. 相似文献