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排序方式: 共有563条查询结果,搜索用时 15 毫秒
91.
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93.
Donatella Pietraforte Eleonora Paulicelli Clarice Patrono Lucrezia Gambardella Giuseppe Scorza Antonella Testa 《Free radical research》2018,52(4):465-479
Reactive oxygen species (ROS) are important mediators of the cytotoxicity induced by the direct reaction of ionising radiation (IR) with all critical cellular components, such as proteins, lipids, and nucleic acids. The derived oxidative damage may propagate in exposed tissues in a dose- and spatiotemporal dependent manner to other cell compartments, affecting intracellular signalling, and cell fate. To understand how cell damage is induced, we studied the oxidative events occurring immediately after cell irradiation by analysing the fate of IR-derived ROS, the intracellular oxidative damage, and the modification of redox environment accumulating in Chinese hamster ovary (CHO) within 1?h after cell irradiation (dose range 0–10?Gy). By using the immuno-spin trapping technique (IST), spectrophotometric methods, and electron paramagnetic resonance (EPR) spectroscopy, we showed that IR-derived ROS (i) induced an IST-detectable, antioxidant-inhibitable one-electron oxidation of specific intracellular proteins; (ii) altered the glutathione (GSH) content (which was found to increase below 2?Gy, and decrease at higher doses, leading to a redox imbalance); (iii) decreased glutathione peroxidase and glutaredoxin activity; (iv) modified neither glutathione reductase nor thioredoxin reductase activity; (v) were detected by spin trapping technique, but adduct intensity decreased due to cell competition for ROS; and (vi) induced no EPR-detectable radicals assignable to oxidised cellular components. In conclusion, our results showed that IR generated an early high oxidising potential (protein radical intermediates, redox imbalance, modified redox enzyme activity) in irradiated cells potentially able to propagate the damage and induce oxidative modification of secondary targets. 相似文献
94.
Akt2, a homolog of Akt1, encodes a serine/threonine protein kinase that is amplified in ovarian and pancreatic cancers. The antiapoptotic activities of the Akt1 proto-oncogene product have been well documented, but the role of Akt2 in cellular survival is poorly understood. Here, we demonstrate that Akt2 mRNA, protein and kinase activity are upregulated during serum deprivation-induced C2C12 cell myogenic differentiation, a process that is associated with the acquisition of an apoptosis-resistant phenotype. Transient transfection of plasmids encoding wild-type and constitutively-active Akt2 conferred resistance against apoptosis in differentiating C2C12 cells, while a kinase-negative Akt2 construct did not. Adenovirus-mediated transfer of the constitutively-active Akt2 cDNA also suppressed apoptosis during serum deprivation-induced myogenic differentiation and it protected cells from apoptosis induced by cell detachment. These data indicate that Akt2 functions as an anti-apoptotic gene during cellular differentiation, a property that may contribute to its oncogenicity. 相似文献
95.
Giovanni Mantovani Vittorio Gebbia Mario Airoldi Cesare Bumma Paolo Contu Alessandro Bianchi Massimo Ghiani Daniela Dessì Elena Massa Luigi Curreli Biancarosa Lampis Paola Lai Carlo Mulas Antonio Testa Ernesto Proto Gabrio Cadeddu Giorgio Tore 《Cancer immunology, immunotherapy : CII》1998,47(3):149-156
We carried out an open, randomized, phase III, multicenter clinical trial to compare, in neo-adjuvant setting, the clinical
response and toxicity of the combination chemotherapy cisplatin + 5-FU with the same combination plus s.c. recombinant interleukin-2
(rIL-2) in patients with advanced (stage III–IV) head and neck squamous-cell carcinoma (HNSCC). Regimen A was the classical
Al Sarraf treatment: 100 mg/m2 cisplatin i.v. on day 1 plus 1000 mg m−2 day−1 5-FU on days 1–5 as a continuous infusion. Regimen B was the same as regimen A plus 4.5 MIU/day rIL-2 s.c. on days 8–12 and
15–19. Treatment was repeated every 3 weeks for three cycles. A total of 33 patients were enrolled in the study; 30 were evaluable
for toxicity and 28 for response. Seventeen patients were assigned to group A and 16 were assigned to group B. Three patients
(20%) of group A and 4 (31%) of group B had a complete response, 9 patients (60%) of group A and 6 (46%) of group B had a
partial response, with an overall response rate of 12 patients (80%) for group A and 10 patients (77%) for group B. Two patients
(13%) of group A and 3 patients (23%) group B had stable disease; 1 patient (7%) of group A had progressive disease. Thus,
there was not a statistically significant difference in response rate between the two groups and therefore there was no benefit
from the addition of immunotherapy with rIL-2 to the standard chemotherapy. Both regimens were well tolerated. There were
2 toxic deaths (6.7%), 1 from hematological causes in group A and 1 from cardiac causes in group B. Myelosuppression and gastrointestinal
toxicity, mainly nausea/vomiting and stomatitis, were the most frequent toxicities. The calculated number of patients for
the sample has not yet been reached; however, the projection of our present results suggests that it is highly improbable
that a clinically significant difference between the two treatment groups will be observed even if the calculated patient
sample size is achieved.
Received: 9 April 1998 / Accepted: 30 June 1998 相似文献
96.
Cell kinetic parameters of mouse granulocytic and mononuclear cells growing in colonies in agar cultures have been measured. Analysis of flash and continuous labelling studies with 3 H-thymidine together with determinations of colony size, growth fraction and mitotic indices, gave the following values for the phases of the cell cycle: G1 = 6·3 1·6 hr, S = 5·8 ± 1·4 hr, G2 = 1·7 ± 0·1 hr and M = 0·7 ± 0·1 hr (42 ± 8 min). No difference in the cell cycle parameters of granulocytic and mononuclear cells were found in this study.
Colonies of different size from cultures of the same age group had similar labelling indices, indicating that the size of a colony is not a function of the rate of proliferation of cells in the colony. Rather, variation in colony size is probably representative of an initial delay in the onset of colony development. 相似文献
Colonies of different size from cultures of the same age group had similar labelling indices, indicating that the size of a colony is not a function of the rate of proliferation of cells in the colony. Rather, variation in colony size is probably representative of an initial delay in the onset of colony development. 相似文献
97.
Asbestos,chromosomal deletions,and tumor suppressor gene alterations in human malignant mesothelioma
Exposure to the carcinogen asbestos is considered to be a major factor contributing to the development of most malignant mesotheliomas (MMs). We highlight the role of asbestos in MM and summarize cytogenetic and molecular genetic findings in this malignancy. The accumulation of numerous clonal chromosomal deletions in most MMs suggests a multistep process of tumorigenesis, characterized by the loss and/or inactivation of multiple tumor suppressor genes (TSGs). Cytogenetic and loss of heterozygosity (LOH) analyses of MMs have demonstrated frequent deletions of specific sites within chromosome arms 1p, 3p, 6q, 9p, 13q, 15q, and 22q. Furthermore, TSGs within two of these regions, i.e., p16/CDKN2A-p14ARF at 9p21 and NF2 at 22q12, are frequently altered in MMs. Homozygous deletion appears to be the major mechanism affecting p16/CDKN2A-p14ARF, whereas inactivating mutations coupled with allelic loss occur at the NF2 locus. Finally, recent studies have demonstrated the presence and expression of simian virus 40 (SV40) in many MMs. SV40 large T antigen has been shown to inactivate the TSG products Rb and p53, suggesting the possibility that asbestos and SV40 could act as cocarcinogens in MM. The frequent occurrence of homozygous deletions of p16/CDKN2A-p14ARF and the ability of SV40 Tag to bind TSG products suggest that perturbations of both Rb- and p53-dependent growth-regulatory pathways are critically involved in the pathogenesis of MM. J. Cell. Physiol. 180:150–157, 1999. © 1999 Wiley-Liss, Inc. 相似文献
98.
Scholten J Hartmann K Gerbaulet A Krieg T Müller W Testa G Roers A 《Transgenic research》2008,17(2):307-315
Mast cells are important effectors of type I allergy but also essential regulators of innate and adaptive immune responses.
The aim of this study was to develop a Cre recombinase-expressing mouse line that allows mast cell-specific inactivation of
genes in vivo. Following a BAC transgenic approach, Cre was expressed under the control of the mast cell protease (Mcpt) 5 promoter. Mcpt5-Cre transgenic mice were crossed to the ROSA26-EYFP Cre excision reporter strain. Efficient Cre-mediated recombination was observed
in mast cells from the peritoneal cavity and the skin while only minimal reporter gene expression was detected outside the
mast cell compartment. Our results show that the Mcpt5 promoter can drive Cre expression in a mast cell-specific fashion. We expect that our Mcpt5-Cre mice will be a useful tool for the investigation of mast cell biology.
Julia Scholten and Karin Hartmann contributed equally to this work.
Supported by grants from the German Research Counsil (Deutsche Forschungsgemeinschaft, RO 2133/2-2) to A.R. and K.H. and the
Koeln Fortune Program/Faculty of Medicine, University of Cologne, to A.R. and K.H.. The authors have no conflict of interest 相似文献
99.
Cornetta T Palma S Aprile I Padua L Tonali P Testa A Cozzi R 《Cell biology and toxicology》2009,25(4):321-330
Oxidative stress seems to play a major role in the pathogenesis of neurodegeneration. In Parkinson’s disease (PD) patients,
the dopaminergic neurons are subjected to oxidative stress resulting from reduced levels of antioxidant defenses such as glutathione
and high amount of intracellular iron. Levodopa (LD) is widely used for the symptomatic treatment of PD, but its role in oxidative
damage control is still unclear. The aim of this study was to analyze the presence of DNA damage in peripheral blood lymphocytes
(PBL) of PD patients, during a washout and a controlled LD dosage and to evaluate the oxidative damage fluctuation after LD
intake. The standard and the Fpg-modified version of Comet assay were applied in analyzing DNA damage in PBL from blood samples
of nine PD patients and nine matched controls. Due to the limited number of patients we cannot reach definite conclusions
even if our data confirm the accumulation of DNA lesions in PD patients; these lesions decrease after LD intake. 相似文献
100.
Michael CW Chan Renee WY Chan Wendy CL Yu Carol CC Ho WH Chui CK Lo Kit M Yuen Yi Guan John M Nicholls JS Malik Peiris 《Respiratory research》2009,10(1):102