全文获取类型
收费全文 | 934篇 |
免费 | 6篇 |
专业分类
综合类 | 1篇 |
化学工业 | 32篇 |
机械仪表 | 8篇 |
矿业工程 | 1篇 |
轻工业 | 4篇 |
水利工程 | 1篇 |
无线电 | 10篇 |
一般工业技术 | 21篇 |
冶金工业 | 858篇 |
自动化技术 | 4篇 |
出版年
2023年 | 5篇 |
2022年 | 4篇 |
2021年 | 5篇 |
2020年 | 4篇 |
2019年 | 2篇 |
2018年 | 2篇 |
2017年 | 1篇 |
2014年 | 6篇 |
2012年 | 6篇 |
2011年 | 6篇 |
2010年 | 2篇 |
2009年 | 3篇 |
2008年 | 2篇 |
2007年 | 3篇 |
2006年 | 4篇 |
2005年 | 1篇 |
2004年 | 3篇 |
2003年 | 5篇 |
2002年 | 1篇 |
2001年 | 1篇 |
2000年 | 3篇 |
1999年 | 32篇 |
1998年 | 275篇 |
1997年 | 137篇 |
1996年 | 91篇 |
1995年 | 55篇 |
1994年 | 62篇 |
1993年 | 52篇 |
1992年 | 4篇 |
1991年 | 7篇 |
1990年 | 4篇 |
1989年 | 6篇 |
1988年 | 6篇 |
1987年 | 9篇 |
1986年 | 9篇 |
1985年 | 4篇 |
1982年 | 3篇 |
1981年 | 2篇 |
1980年 | 10篇 |
1978年 | 2篇 |
1977年 | 24篇 |
1976年 | 66篇 |
1975年 | 3篇 |
1974年 | 1篇 |
1971年 | 1篇 |
1966年 | 1篇 |
1960年 | 1篇 |
1955年 | 4篇 |
排序方式: 共有940条查询结果,搜索用时 15 毫秒
1.
LW Seymour H Soyez A De Marre MA Shoaibi EH Schacht 《Canadian Metallurgical Quarterly》1996,11(5):351-365
Prodrugs of mitomycin C (MMC) based on soluble poly-[N-(2-hydroxyethyl)-L-glutamine] (pHEG) polymers have been evaluated as tumour-targeted drugs. These materials are designed to exploit the enhanced permeability of tumour vasculature, combining a passive tumour tropism with decreased systemic liberation of free MMC. A tri- or tetrapeptide linkage (e.g. Gly-Phe-Ala-Leu) between pHEG and the aziridine nitrogen of MMC can combine good hydrolytic stability with rapid cleavage by lysosomal enzymes, releasing free MMC. The conjugates showed decreased systemic toxicity and could be administered to mice at a total MMC dose of 15 mg/kg i.v., compared with just 6 mg/kg for free MMC. Conjugates also showed better activity against animal models of established tumours, achieving up to 77% increased life span (ILS) against solid P388 leukaemia, compared with only 23% for free MMC, and up to 121% ILS against solid C26 colorectal carcinoma, compared with no activity for the free drug. Improving the therapeutic index of anticancer drugs by combining tumour tropism with decreased systemic toxicity is a versatile approach that should produce a new generation of improved anticancer agents. 相似文献
2.
EH Eddes AM Masclee HG Gooszen M Fr?lich CB Lamers 《Canadian Metallurgical Quarterly》1997,174(4):387-392
Two mobilizable cloning vectors, designated pABW1 and pAWB2, were constructed basing on the E. coli vector pBGS18 and oriT originating from RK2. In pABW2 the kanamycin resistance gene was replaced by a novel tetracycline resistance cassette derived from Tn1721. Both vectors, specific for E. coli, allow to perform the cloning steps in E. coli and then to efficiently transfer the constructs by conjugation to the host of choice. A vector which cannot propagate in the given host can be applied for identification of the host specific plasmid replicator regions. With the use of pABW2 we defined the minimal replicator region of pTAV202-a mini-derivative of the large pTAV1 plasmid of P. versutus. We also proved that RepC' encoded on this fragment is the principal initiator replication protein and that oriV is located along its coding sequence. 相似文献
3.
4.
The EU Concerted Action Workshop on 11q23 Abnormalities in Hematological Malignancies collected 550 patients with abnormalities involving 11q23. Of these, 53 patients had a translocation involving chromosome 11, breakpoint q23, and chromosome 19, breakpoint p13. Karyogram review enabled each patient to be further defined as t(11;19)(q23;p13.1) (21 patients) or t(11;19)(q23;p13.3) (32 patients). There was a marked difference between the type of banding and the translocation identified: t(11;19)(q23;p13.1) was detected predominantly by R-banding, whereas t(11;19)(q23;p13.3) was detected almost solely by G-banding. Additional change was extremely rare in patients with t(11;19)(q23;p13.1) but occurred in nearly half of the patients with t(11;19)(q23;p13.3). Patients with t(11;19)(q23;p13.1) all had leukemia of a myeloid lineage, mostly acute myeloid leukemia (AML), and were predominantly adult. In contrast patients with t(11;19)(q23;p13.3) had malignancies of both myeloid and lymphoid lineage and were mainly infants less than 1 year old. The survival of both groups of patients was generally poor, over 50% of t(11;19)(q23;p13.1) patients died within 2 years of diagnosis and the median survival of acute lymphoblastic leukemia (ALL) patients with t(11;19)(q23;p13.3) was 17.6 months. 相似文献
5.
EH Jeffery K Abreo E Burgess J Cannata JL Greger 《Canadian Metallurgical Quarterly》1996,48(6):649-665
Although the full mechanisms are not yet elucidated, research into the mechanism of toxicity of aluminum (Al) on bone formation and remodeling and on hematopoietic tissue is ongoing. In contrast little information exists on the interactive effects of systemic Al and the kidney. In bone, both clinically and experimentally, high doses of Al inhibit remodeling, slowing both osteoblast and osteoclast activities and producing osteomalacia and adynamic bone disease. In contrast, while very low levels of Al are mitogenic in bones of experimental animals, the effect of low levels of Al in humans is unknown. Aluminum has been shown to have its mitogenic action at the osteoblast, but whether the effect on resorption is viz osteoblast-directed changes in osteoclast activity has not yet been determined. Parathyroid hormone (PTH) levels are disrupted by Al in humans and animals. Whether altered PTH levels play a major or even a minor role in Al-dependent osteotoxicity requires clarification. In hematopoietic tissue, Al causes a microcytic anemia, not reversible by iron. Friend leukemia cells treated with Al have been reported to accumulate excess iron, without incorporating it into ferritin or heme. It is not yet known which steps in iron metabolism are disrupted by Al, if they involve a single mechanism of action, or even if this disruption in iron metabolism accounts for the anemia seen in Al toxicosis. In kidney, research is needed to evaluate Al nephrotoxicity; there are almost no studies in this area. Furthermore, research is needed to evaluate mechanisms of renal Al excretion, presently shown by one study to occur at the distal tubule. Such studies might well throw light on whether Al plays a role in aggravating renal insufficiency, or whether the role of the kidney in Al toxicosis is limited to the causative effect of renal compromise on Al accumulation. In summary, while a number of mechanisms have been proposed for the toxic action of Al, no single mechanism emerges to explain these diverse effects of systemic Al. Recommendations for future research are presented and summarized in Table 1. 相似文献
6.
7.
S Whitman L Lacey D Ansell EH Chen J Dell CW Phillips 《Canadian Metallurgical Quarterly》1993,22(3):393-397
Magnetic resonance imaging allows a noninvasive assessment of myelination during normal brain maturation as well as the detection of genetically determined and acquired diseases that affect the synthesis and maintenance of myelin. If this high sensitivity of magnetic resonance imaging for white matter changes is completed by adequate clinical and biochemical information, a unique diagnostic tool is available to gain new insights in the formation of myelin and pathogenesis of myelin disorders. 相似文献
8.
A Saleem N Ibrahim M Patel XG Li E Gupta J Mendoza P Pantazis EH Rubin 《Canadian Metallurgical Quarterly》1997,57(22):5100-5106
Camptothecins are a new class of anticancer drugs that target DNA topoisomerase I; current efforts are directed toward elucidating optimal combinations of these drugs with other antineoplastic agents. A rationale for the use of sequential therapy involving the combination of camptothecins with topoisomerase II-targeting drugs, such as etoposide, has arisen from observations of increased topoisomerase II protein levels in cell lines resistant to camptothecin. In an effort to understand potential mechanisms of resistance to this strategy, we developed a U-937 cell subline, denoted RERC, that is capable of surviving exposure to sequential topoisomerase poisoning. The RERC cells are 200-fold resistant to camptothecin, 8-fold resistant to etoposide, and 10-fold hypersensitive to cisplatin compared to the parental U-937 cells. Biochemical analyses indicate that the resistant phenotype involves alterations in both topoisomerase I and topoisomerase IIalpha. Topoisomerase I catalytic activity in the resistant cells is similar to that of the parental line but is resistant to camptothecin. Moreover, the resistant cells express a single mRNA species of topoisomerase I that codes for a mutation in codon 533. In addition, topoisomerase IIalpha protein levels are decreased 10-fold in the resistant line, coincident with a two-fold decrease in the expression of topoisomerase IIalpha mRNA. Collectively, these results indicate that resistance to sequential topoisomerase poisoning may involve a reduction in total cellular topoisomerase activity. 相似文献
9.
10.
PURPOSE: Previous research has demonstrated that testosterone therapy causes a profound suppression of autoimmune disease in lacrimal glands of female mouse models of Sj?gren's syndrome. The aim of the present study was to determine whether other anabolic androgens, nonandrogenic steroids, or immunosuppressive agents might duplicate this hormonal effect. For comparative purposes, we also evaluated the influence of these various pharmacologic compounds on the tear volume, the magnitude of lymphocyte infiltration in the submandibular gland, and the extent of mucosal and peripheral lymphadenopathy. METHODS: Female MRL/MpJ-lpr/lpr mice were administered vehicle, steroids, or immunosuppressive compounds for 21 days after the onset of disease. Lacrimal glands and tears, as well as submandibular glands, spleens, and superior cervical and mesenteric lymph nodes were collected immediately before or after treatment and then processed for analysis. RESULTS: Our results showed that: (1) the immunosuppressive impact of testosterone on lymphocyte infiltration in lacrimal tissue was reproduced by the administration of 19-nortestosterone or cyclophosphamide, but not by therapy with 17 beta-estradiol, danazol, the experimental steroid Org 4094, cyclosporine A or dexamethasone; (2) treatment with testosterone, 19-nortestosterone, cyclophosphamide, or dexamethasone significantly reduced the extent of inflammation in salivary glands; (3) exposure to cyclophosphamide markedly diminished the size of lymphatic and splenic tissues, whereas glucocorticoid treatment only decreased the weight of superior cervical lymph nodes; and (4) administration of 17 beta-estradiol, Org 4094, or dexamethasone led to a significant decrease in tear volume. CONCLUSIONS: Overall, these results demonstrate that androgen or cyclophosphamide therapy may successfully ameliorate autoimmune expression in lacrimal and salivary glands of a female mouse model of Sj?gren's syndrome. 相似文献