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81.
Zbigniew Darzynkiewicz 《Journal of cellular biochemistry》1995,58(2):151-159
There is a strong evidence that administration of antitumor drugs triggers apoptotic death of target cells. A characteristic feature of appotosis is active participation of the affected cell in its demise. Attempts have been made, therefore, to potentiate the cytotoxicity of a variety of agents by modulating the propensity of cells to respond by apoptosis. Several strategies to enhance apoptosis that involve modulation of the cell cycle or differentiation are discussed. Loss of control of the G1 checkpoint in tumor cells allows one to design treatments that arrest normal cells at the checkpoint and attempt to selectively kill tumor cells with S phase specific drugs. The possibility of a restoration of the apoptosis triggering function of the tumor suppressor gene p53 when the G1 checkpoint function is abolished is expected to increase tumor cells' sensitivity to S phase poisons. Because induction of apoptosis by many antitumor drugs is cell cycle phase specific, drug combinations that preferentially trigger apoptosis at different phases of the cycle, or recruitment of cells to the sensitive phase, offer another antitumor strategy. There is also evidence that apoptosis is potentiated when cell differentiation is triggered follwing DNA damage. This observation suggests that strategies which combine DNA damaging and differentiating drugs, under conditions where the latter are administered following DNA damage caused by the former, may be successful. 相似文献
82.
Tumor promoters, proinflammatory cytokines, endotoxins, and protein synthesis inhibitors can modulate cell cycle kinetics of various cell types, stimulate production of reactive oxygen species, and induce keratinocytes to produce interleukin-8 (IL-8), a potent chemotactant for polymorphonuclear neutrophils and T lymphocytes. The aim of this study was to determine whether perturbations of cytogenetic responses correlated with the induction of IL-8 expression. Cultures of primary human keratinocytes were grown in serum-free medium with 5 mol/L bromodeoxyuridine to label DNA and exposed either to phorbol-13-myristate-12-acetate (PMA) (0.0001–100 ng/ml), cycloheximice (CHX) (0.01–50 g), lipopolysaccharide (0.1–100 g/ml), tumor necrosis factor- (TNF) (3.13–50 ng/ml), or interleukin-1 (IL-1) (1–182 pg/ml). Metaphase chromosome preparations were stained by a fluorescence-plus-Giemsa technique to differentiate sister chromatids. For IL-8 production, keratinocytes were grown to 70% confluency and then exposed to chemicals for 24 h. Immunoreactive IL-8 was quantitated from the supernatants by ELISA. With the exception of benzo(a)pyrene used as a positive control, none of the agents induced sister chromatid exchanges. However, PMA and TNF induced IL-8 production that coincided with significant cell cycle inhibition. IL-1 had no effect on cytogenetic endpoints, yet stimulated a 6.3-fold increase in IL-8. CHX inhibited cell cycle progression and mitotic activity at concentrations that were 200 times lower than required for IL-8 induction; however, puromycin (0.31–10 g/ml), another protein synthesis inhibitor, did not induce IL-8. At all concentrations tested, TNF reduced the mitotic index by 45%, slowed cell cycle progression by 3.5 h, and induced a flat, albeit large, IL-8 response at concentrations 12.5 ng/ml. These agent-specific response patterns suggest that induction of IL-8 production is not always the inevitable result of cell cycle perturbations or genetic damage.Abbreviations B(a)P
benzo(a)pyrene
- BrdU
5-bromo-2-deoxyuridine
- CHX
cycloheximide
- ICAM
intercellular adhesion molecules
- IL-1
interleukin-1
- IL-8
interleukin-8
- KGM
keratinocyte growth medium
- LPS
lipopolysaccharide
- PKC
protein kinase C
- PMA
phorbol-13-myristate-12-acetate
- PMN
polymorphonuclear neutrophil
- ROS
reactive oxygen species
- SCE
sister chromatid exchange
- TNF
tumor necrosis factor 相似文献
83.
84.
综述了近年来有关利用基因转移技术修饰肿瘤细胞制备肿瘤基因工程疫苗的最新研究进展,着重阐述了逆转录病毒载体介导的基因转移及其安全性;归纳了目前可用于肿瘤基因工程疫苗的各种目的基因的特点及作用并对这类肿瘤疫苗制备过程中所存在的问题进行了分析. 相似文献
85.
Biological activities of chemically synthesized analogues of the nonreducing sugar moiety of lipid A 总被引:12,自引:0,他引:12
M Matsuura Y Kojima J Y Homma Y Kubota A Yamamoto M Kiso A Hasegawa 《FEBS letters》1984,167(2):226-230
Adriamycin-Fe3+ complex catalyzes the formation of hydroxyl radical from hydrogen peroxide but the DNA-adriamycin-iron ternary complex is much more effective. 11-Deoxyadriamycin, which shows no spectral evidence of complex formation with iron, was ineffective. The generation of hydroxyl radical by adriamycin-Fe3+ complex in the presence of DNA correlates with its ability to cleave DNA. Hydroxyl radicals are thus implicated as the reactive oxygen species involved in the DNA damage caused by the adriamycin-Fe3+ complex. 相似文献
86.
G. M. S. van Slogteren P. J. J. Hooykaas R. A. Schilperoort 《Plant molecular biology》1984,3(6):333-336
Summary A shooty tumor induced by a shooter mutant of an octopine strain of Agrobacterium tumefaciens was cloned. One clone obtained (TS038) behaved aberrantly in that it grew as a shooty tumor tissue on phytohormone free medium, but did not contain octopine synthase activity. In line TS038 the genes for octopine synthase and for the enzymes involved in agropine and mannopine synthesis were present, but were not transcribed. However, the above genes became active in TS038 tumor shoots after grafting as well as after treatment with the hypomethylating agent 5-azacytidine. After an unusually long incubation period in the growth cabinet shoot cultures appeared to have developed small shoots from the top of the leaves. This unusual form of differentiation was found to be accompanied by the induction of octopine synthase activity. 相似文献
87.
John C. Angello Howard L. Hosick 《Biochemical and biophysical research communications》1982,107(3):1130-1137
Multicellular aggregates of tumorigenic mouse mammary epithelial cells contain a hyaluronate-rich matrix, both at the aggregate periphery and within the growing spheroid. It is proposed that the establishment of a hyaluronaterich matrix is essential to spheroid growth in vitro, and that the spheroid is a good model system for analysis of this aspect of early tumor development. 相似文献
88.
W.James Nelson Constantin E. Vorgias Peter Traub 《Biochemical and biophysical research communications》1982,106(4):1141-1147
A new method is described for the purification of the intermediate filament protein vimentin from Ehrlich ascites tumor cells using single-stranded DNA-cellulose affinity chromatography. The procedure is rapid and allows the large scale isolation of the protein. Partial characterization of vimentin shows that it has a molecular weight of 58000 and an apparent pI of 5.3. It can be degraded by the vimentin-specific, Ca2+-activated proteinase which results in the production of a characteristic set of degradation products. The vimentin also cross-reacts with the intermediate filament protein monoclonal antibody, α-IFA. 相似文献
89.
Thomas E. Gray David G. Thomassen Marc J. Mass J. Carl Barrett 《In vitro cellular & developmental biology. Plant》1983,19(7):559-570
Summary A cell culture system is described for the growth of rat tracheal epithelial (RTE) cells at clonal density. The system uses
normal, early passage RTE cells grown on feeder layers of lethally irradiated 3T3 cells. The RTE cells have a high colony
forming efficiency (5 to 10%) in culture, can be passaged up to 5 times, and are capable of more than 20 cumulative doublings
per colony forming cell. The epithelial nature of the cells was confirmed by cell and colony morphology, immunoperoxidase
staining of intracellular keratin, and cellular ultrastructural studies. The cytotoxic response of RTE cells to a variety
of carcinogens, including a direct acting chemical carcinogen, a physical carcinogen, and a series of polycyclic aromatic
hydrocarbons, was quantitated. A linear decrease in the logarithm of survival was observed with increasing doses ofN-methyl-N′-nitro-N-nitrosoguanidine (MNNG), γ-irradiation, 7,12-dimethylbenz(a)anthracene, and a diol-epoxide of benzo(a)pyrene. No toxicity was observed after treatment with benzo(a)pyrene or 3-methylcholanthrene over the concentration range examined. In contrast, phorbol ester tumor promoters stimulated
cell growth markedly. Based on these and other studies, the RTE cell culture system represents a model system that will be
useful for quantitative studies of epithelial cell growth, differentiation, and carcinogenesis. 相似文献
90.
转移及非转移肿瘤移植后615小鼠血液流变学变化的研究 总被引:1,自引:0,他引:1
血道高转移瘤株FC、淋巴合并血道高转移瘤株U14、淋巴道高转移瘤株H22、非转移瘤株P615分别接种于336只纯系近交615小鼠.不同时间取血并处死动物,进行组织学及血液流变学检查.将转移瘤发展过程分为潜伏期、侵袭期、转移早、中、晚期,非转移瘤发展过程分为潜优期、增殖期、囊腔形成期及中心坏死期.本实验结果显示,不同转移能力及途径肿瘤发展的不同时期血液流变学变化规律不同,因而表明肿瘤侵袭、转移与血液流变学变化之间存在互为因果的紧密关系.其临床诊断及治疗意义被讨论. 相似文献