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1.
Andries S. Koster 《Pharmacy World & Science》1991,13(3):123-126
Quinones can be metabolized by various routes: substitution or reductive addition with nucleophilic compounds (mainly glutathione and protein thiol groups), one-electron reduction (mainly by NADPH: cytochrome P-450 reductase) and two-electron reduction (by D,T-diaphorase). During reduction semiquinone radicals and hydroquinones are formed, which can transfer electrons to molecular oxygen, resulting in the formation of reactive oxygen intermediates and back-formation of the parent quinone (redox cycling). Reaction of semiquinones and reactive oxygen intermediates with DNA and other macromolecules can lead to acute cytotoxicity and/or to mutagenicity and carcinogenicity. The enhanced DNA-alkylating properties of certain hydroquinones are exploited in the bioreductive alkylating quinones. Acute cytotoxicity of quinones appears to be related to glutathione depletion and to interaction with mitochondria and subsequent disturbance of cellular energy homoeostasis and calcium homoeostasis. These effects can to a certain extent be predicted from the electron-withdrawing and electron-donating effects of the substituents on the quinone nucleus of the molecule. Prediction of cytostatic potential remains much more complicated, because reduction of the quinones and the reactivity of the reduction products with DNA are modulated by the prevailing oxygen tension and by the prevalence of reducing enzymes in tumour cells.This article is based on a lecture given at the 16th LOF Symposium, 27 October 1989, Utrecht, the Netherlands. 相似文献
2.
Ramona A. Cole Anita Bansal Debra M. Moriarity William A. Haber William N. Setzer 《Journal of natural medicines》2007,61(4):414-417
The leaf essential oil of Eugenia zuchowskiae from Monteverde, Costa Rica, has been obtained by hydrodistillation and analyzed by GC–MS. The principal constituents of
E. zuchowskiae leaf oil were α-pinene (28.3%), β-caryophyllene (13.2%), α-humulene (13.1%), and α-copaene (8.1%). The leaf essential oil
of E. zuchowskiae showed pronounced in-vitro cytotoxic activity against MCF-7, MDA-MB-468, and UACC-257 human tumor cell lines. The major components
showed cytotoxic activities comparable to doxorubicin (LC50 14–70 μg/ml). 相似文献
3.
Dr. David M. Euhus MD Lucille Kimura PhD Bruce Arnold MD 《Annals of surgical oncology》1997,4(5):432-439
Background: Mice immunized with murine mammary carcinoma cells genetically engineered to secrete interleukin-2 (IL-2) are rendered resistant
to subsequent challenge with unmodified tumor cells, and in the case of mice bearing established tumors, the rate of development
of pulmonary metastases is reduced. Despite these encouraging animal results, little is known about the induction of antitumor
immunity by IL-2 gene transfer in human breast cancer.
Methods: Adenovirally mediated IL-2 gene transfer was performed in 12 tumor fragment cultures established from seven primary breast
cancers. Autologous tumor infiltrating lymphocytes (TILs) or peripheral blood mononuclear cells (PBMCs) were cocultured with
transduced tumor fragments, and changes in phenotype and cytotoxicity were measured.
Results: IL-2 was never detectable in the untransduced cultures, but it peaked at 5.0—1,324.8 ng/ml in the transduced cultures. Lymphocyte
counts declined in all untransduced cultures, but they increased two- to sevenfold in four transduced cultures. CD4:CD8 ratios
decreased from a mean of 2.11 at baseline to 1.27 after stimulation in coculture (p=0.03). Expansion of lymphocytes expressing
the natural killer cell phenotype (CD3−CD56+) occurred in only one culture, but the CD3+CD56+ population increased in four of six cultures. Lymphocytes from four of 10 cocultures generated significant cytotoxicity against
allogeneic breast cancer cells. Induction of cytotoxicity correlated with expansion of the CD3+CD56+ phenotype (R2=0.805, p=0.02).
Conclusions: IL-2 gene expression by human breast cancer causes expansion of CD3+CD56+ cytotoxic lymphocytes. This phenotype is consistent with that of a non-major histocompatibility complex (MHC)-restricted
cytokine induced killer cell population previously described.
Opinions, interpretations, conclusions and recommendations are those of the author and are not necessarily endorsed by the
U.S. Army.
Presented at the 49th Annual Cancer Symposium of The Society of Surgical Oncology, Atlanta, Georgia, March 21–24, 1996. 相似文献
4.
The cytotoxicity of extracts from rice cultures of five Fusarium avenaceum strains against the porcine epithelial kidney cell-line PK-15 was investigated using the Alamar Blue™ assay. After the identification of known fungal metabolites, cytotoxic extracts were fractionated using semi-preparative reversed-phase HPLC and normal phase LC, and the fractions were tested for cytotoxicity. In this way, two different groups of metabolites were identified as the major cytotoxic principles of the extracts. High concentrations of enniatins, especially enniatins B and B1, inhibited the metabolic activity of PK-15 cells. Furthermore, an unidentified metabolite, produced in high amounts by a strain that produced relatively small amounts of enniatins, was also found to be cytotoxic to PK-15 cells. This study shows that enniatins, a group of cyclic depsipeptides, which have been ignored as significant contributors to the toxicity of fungal extracts, may account for most of the observed effect for F. avenaceum. 相似文献
5.
The cytotoxic effects of propyl gallate (PG), its related gallates and gallic acid have been studied in freshly isolated
rat hepatocytes. Addition of PG (0.5–2.0 mM) to hepatocyte suspension elicited concentration-dependent cell death accompanied
by losses of intracellular ATP, adenine nucleotide pools, glutathione (GSH) and protein thiols. The rapid loss of intracellular
ATP preceded the onset of cell death caused by PG. In the comparative toxic effects of PG and related gallates at concentration
of 1 mM, octyl gallate (OG), dodecyl gallate (DG) and butyl gallate (BG) elicited an abrupt depletion of ATP, followed by
an acute cell death. These gallates were more toxic than PG; the toxic effects of PG were similar to those of methyl gallate
(MG) and ethyl gallate (EG). In mitochondria isolated from rat liver, PG caused a concentration-dependent increase in the
rate of state 4 oxygen consumption, indicating an uncoupling effect. The rate of state 3 oxygen consumption was inhibited
by OG and DG. According to the respiratory control index, the order of impairment potency to mitochondria was OG>BG, DG>PG>EG,
MG>gallic acid. These results indicate that PG and related gallates are toxic to hepatocytes and that the acute cytotoxicity
may be due to mitochondrial dysfunction.
Received: 16 May 1994 / Accepted: 15 August 1994 相似文献
6.
N. Torlone A. Piazza M. Valeri P. I. Monaco L. Provenzani E. Poggi D. Adorno C. U. Casciani 《Transplant international》1992,5(Z1):S676-S678
Donor-specific anti-HLA antibodies were studied by cytotoxicity crossmatching (CTXM) and flow cytometry crossmatching (FCXM) in 117 kidney transplant candidates; the same study was carried out in 33 cadaver-donor kidney recipients, during the first 3 post-transplant months, for which donor cells were available. Pre-transport evaluation showed that 82.9 % of subjects were CTXM negative/FCXM negative, 6.8 % of patients were positive in both tests, and 10.3 % were CTXM negative/FCCM positive. Post-transplant monitoring for donor-specific antibodies (Abs-DS) showed that nine recipients (27.3 %) were FCXM positive; six of them were IgG + and three IgM +. In comparing these results with the clinical course, a significant association between FCXM IgG + and rejection episodes was observed (P < 0.01). 相似文献
7.
胆道支撑管显影材料的制备及体外细胞毒性评价 总被引:4,自引:0,他引:4
目的 探讨新型显影胆道支撑管材料制备的可行性,对构建出的材料进行体外细胞毒性评价和筛选。方法 选择具有X线下显影特性的基础材料A、B、C,分别与硅橡胶生胶共混炼,模压后分别得到相应的显影复合材料甲、乙、丙,经一段和二段硫化过程完成加工。采用MTT法作为体外细胞毒性评价的方法,测定参比对照材料和新材料的50%浓度的浸提液对小鼠成纤维细胞的增殖率的影响,确定细胞毒性级别。结果 新材料甲、乙、丙在x线下影像清晰。甲、乙材料的细胞毒性级别为零,丙材料细胞毒性级别为2。结论 构建出在X线下显影的弹性体材料可行。材料甲、乙是制造新型胆道支撑管的初选材料,材料丙无应用的价值。 相似文献
8.
聚—DL—乳酸复合材料的细胞毒性评价 总被引:2,自引:0,他引:2
孙皎 《口腔材料器械杂志》1998,7(2):66-67
本文对新研制的聚-DL-乳酸可吸收复合材料进行细胞毒性的实验研究,采用L-929小鼠成纤维细胞,经材料浸提液与细胞接触2、4、7 天后,在分光光度仪下测定光吸收度,以评价材料的细胞毒性.结果表明;该材料对培养细胞无明显细胞毒性刺激作用,细胞生长良好,各期实验组的细胞增殖状况与阴性对照组相似. 相似文献
9.
The Effects of Serum from Patients with Acute Liver Failure on the Growth and Metabolism of Hep G2 Cells 总被引:6,自引:0,他引:6
In many bioartificial liver systems currently being designed and evaluated for use in fulminant hepatic failure, direct contact is required between the patient's blood and the liver cells in the device. The efficacy of such devices will be influenced by the interaction of fulminant hepatic failure (FHF) patient serum with the cells. We have found that FHF serum inhibits the growth rate and the synthesis of DNA, RNA, and protein; disturbs glutathione homeostasis; and induces morphological changes in cultured human Hep G2 cells. These interactions should influence the design of bioartificial liver devices based on proliferating cell lines and indicate the requirement to pretreat FHF patient plasma to reduce the toxin load. 相似文献
10.