首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   450篇
  免费   26篇
  2022年   1篇
  2021年   3篇
  2020年   2篇
  2019年   1篇
  2018年   4篇
  2017年   4篇
  2016年   10篇
  2015年   15篇
  2014年   13篇
  2013年   21篇
  2012年   33篇
  2011年   38篇
  2010年   17篇
  2009年   19篇
  2008年   37篇
  2007年   34篇
  2006年   22篇
  2005年   18篇
  2004年   23篇
  2003年   25篇
  2002年   30篇
  2001年   1篇
  2000年   4篇
  1999年   6篇
  1998年   10篇
  1997年   6篇
  1996年   7篇
  1995年   4篇
  1994年   4篇
  1993年   5篇
  1992年   4篇
  1991年   2篇
  1990年   1篇
  1989年   4篇
  1988年   3篇
  1987年   5篇
  1985年   5篇
  1984年   5篇
  1983年   4篇
  1982年   3篇
  1981年   6篇
  1980年   9篇
  1979年   1篇
  1975年   1篇
  1974年   1篇
  1973年   2篇
  1972年   2篇
  1971年   1篇
排序方式: 共有476条查询结果,搜索用时 15 毫秒
471.
Proliferating cell nuclear antigen (PCNA) monomers assemble to form a ring-shaped clamp complex that encircles duplex DNA. PCNA binding to other proteins tethers them to the DNA providing contacts and interactions for many other enzymes essential for DNA metabolic processes. Most eukarya and euryarchaea have only one PCNA homolog but Thermococcus kodakarensis uniquely has two, designated PCNA1 and PCNA2, encoded by TK0535 and TK0582, respectively. Here, we establish that both PCNA1 and PCNA2 form homotrimers that stimulate DNA synthesis by archaeal DNA polymerases B and D and ATP hydrolysis by the replication factor C complex. In exponentially growing cells, PCNA1 is abundant and present at an ~100-fold higher concentration than PCNA2 monomers. Deletion of TK0582 (PCNA2) had no detectable effects on viability or growth whereas repeated attempts to construct a T. kodakarensis strain with TK0535 (PCNA1) deleted were unsuccessful. The implications of these observations for PCNA1 function and the origin of the two PCNA-encoding genes in T. kodakarensis are discussed.  相似文献   
472.
Summary In the present study, we investigated the ability of epidermal growth factor (EGF), insulin-like growth factor-1 (IGF-1), and insulin to protect the human breast cancer cell line MDA-231 from death induced by the antitumor drug actinomycin D (ACT-D). ACT-D is an inhibitor of RNA and protein synthesis, and its cytotoxicity may result due to continuous depletion in some vital protein molecules. Cell death was induced in the MDA-231 cells by either continuous exposure to a low dose of ACT-D (0.2μg/ml), or by a short-time exposure to a high dose of ACT-D (2μg/ml) and further culturing in the absence of the drug. Cell death was evaluated by the trypan blue dye exclusion test, the release of lactic dehydrogenase into the culture medium, and the depletion in the cellular ATP content. EGF and IGF-1, each at an optimal concentration of 20 ng/ml, enhanced substantially survival of cells exposed either to a low or a high dose of ACT-D. The combination of EGF (10 ng/ml) and IGF-1 (10 ng/ml) had an additive survival effect, which proposes that each of the growth factors enhanced survival by a distinct pathway. Insulin up to 40 ng/ml had no effect on cell survival. Pretreatment of the cells for 1 to 5 h with EGF and IGF-1 protected cells from the cytotoxic effect of ACT-D. Exposure of the cells to 2μg/ml of ACT-D for 1 h resulted in a drastic inhibition in uridine incorporation and only in a slight inhibition in leucine incorporation. Further incubation in the absence of ACT-D resulted in a continuous decrease in uridine and in leucine incorporation, either in the absence or presence of the growth factors. However, EGF and IGF-1, but not insulin, attenuated significantly this continuous decrease. We assume that EGF and IGF-1 protect cell viability by a mechanism that maintains a critical level of some vital protein molecule above the critical level at which cells die. Our finding that EGF and IGF-1 induced resistance to ACT-D suggests that growth factors may be involved in the mechanism of drug resistance.  相似文献   
473.
A procedure is described for the preparation of purified membranes from late-exponential or stationary phase cells ofMycoplasma gallisepticum. NonenergizedM. gallisepticum cells were lysed in an isosmotic NaCl-Tris buffer at pH 8.5, conditions that seem to interfere with cell volume regulation. Electron microscopy, chemical, density gradient, and enzymatic analyses of the membrane preparation showed the membranes to be free of cytoplasmic contaminants and partially sealed.  相似文献   
474.
The responses to PAR intensity and nitrogen deficiency have been investigated in the Δ5‐desaturase‐deficient mutant (P127) of the microalga Parietochloris incisa (Reisigl) Shin Watan. (Chlorophyta, Trebouxiophyceae). The mutant accumulates dihomo‐γ‐linolenic acid (DGLA, C20:3 ω6) instead of arachidonic acid (C20:4 ω6) characteristic of the wildtype. The growth, fatty acid and pigment composition, and light absorption by P127 cell suspensions were studied for the first time during cultivation on complete and N‐free BG‐11 medium at 35, 130, and 270 μE · m?2 · s?1. On complete medium under high irradiance, an increase in biomass was observed, and total fatty acid (TFA) and DGLA contents were higher than in N‐starving cultures. A distinct irradiance‐dependent rise in carotenoid‐to‐chl ratio was recorded in P127 due to an increase in carotenoids (on complete medium) or by a decline in chl (on N‐free medium). Cultivation under high and medium irradiances caused a decline in light‐harvesting xanthophylls and an increase in β‐carotene, localized predominantly in cytoplasmic oil bodies (OB). The P127 mutant, similar to wildtype, responded to the stresses by coordinated induction of fatty acid and carotenoid syntheses, but displayed the same magnitude of the response as was observed in wildtype under 30% lower irradiance. The changes in optical properties of the P127 cultures tightly correlated with their pigment composition, and hence with fatty acid content, making it possible to develop a nondestructive technique for the assay of TFA and DGLA. The peculiarities of the stress responses in the wildtype and the mutant are discussed.  相似文献   
475.
Abstract. Pieces cut from colonies of the soft coral Dendronephthya hemprichi exhibited rapid and effective attachment to hard surfaces. Attachment involved development of root-like processes (RLPs), which appeared at the basal part of the fragment 4 days after its removal from the colony. The fine structural changes and cascade of cellular events occurring in the RLP before and after attachment were studied using SEM, TEM, and LM. The epidermis of the RLPs is actively involved in the attachment process and several distinct phases are documented: appearance of numerous oval vesicles, extrusion of these vesicles resulting in the formation of an outer layer composed of extracellular organic matrix and organellar debris, which functions as an adhesive device leading to initial attachment. The latter phase was followed by the formation of desmocytes, which develop in the RLP epidermis and function as anchoring devices, mediating the firm attachment of the fragment to the substrate. This is the first evidence among anthozoans that desmocytes play an active role in anchoring tissue to substrate and thus extends the range of functions exhibited by desmocytes among anthozoans.  相似文献   
476.
A high fat diet fed ad libitum will promote breast tumorigenesis in rats while caloric restriction of the same high fat diet counteracts this promotional effect. The present study examined the effects of dietary fat and calorie intake on adipose tissue weight and fatty acid composition and on tumor incidence and development. The sites of adipose tissue chosen were the mammary fat pad, representing adipose tissue in the immediate location of the studied tumor, and the abdominal fat depot which in humans has been associated with an increased risk of breast cancer. High (20% corn oil) and low (5% corn oil) fat test diets were offered ad libitum and at 40% restriction levels. In agreement with prior studies, caloric restriction of both high and low fat diets led to marked decreases in tumor incidence (63 to 68% versus 21%), tumor burden (1.84 to 2.05 versus 0.37 to 0.43 tumors/rat), and tumor weight (7.1 to 11.9 versus 1.4 to 2.2 g) at the time of sacrifice (133 days post-DMBA). While final body weights were reduced in proportion to the level of caloric restriction (290 to 291 g versus 184 to 201 g), abdominal fat (8.8 to 9.2 versus 0.9 to 1.6 g), and mammary fat weights (3.1 to 4.1 versus 0.7 to 2.0 g) were reduced markedly in association with the decrease in tumorigenesis. While both tumor and mammary fat were enriched with linoleate reflecting the fatty acid composition of dietary fat, the ratio of arachidonic acid to linoleic acid was higher in tumor tissue than in surrounding normal mammary tissue in both the phospholipid (0.78 versus 0.18) and neutral lipid fractions (0.22 versus 0.03). These observations are consistent with the concept that increases in fat tissue mass in abdominal and mammary fat depots may mediate some of the promotional effects of high fat and high calorie diets. Restriction of dietary fat and calories to reduce body fat and strategies to modify the composition of stored lipids in fat depots may offer nutritional approaches to breast cancer prevention and treatment.  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号