全文获取类型
收费全文 | 121篇 |
免费 | 14篇 |
出版年
2021年 | 1篇 |
2019年 | 2篇 |
2018年 | 1篇 |
2016年 | 2篇 |
2015年 | 4篇 |
2014年 | 2篇 |
2013年 | 16篇 |
2012年 | 5篇 |
2011年 | 8篇 |
2010年 | 7篇 |
2009年 | 4篇 |
2008年 | 4篇 |
2007年 | 5篇 |
2006年 | 7篇 |
2005年 | 5篇 |
2004年 | 3篇 |
2003年 | 5篇 |
2002年 | 3篇 |
2001年 | 4篇 |
2000年 | 3篇 |
1999年 | 1篇 |
1998年 | 4篇 |
1997年 | 4篇 |
1996年 | 4篇 |
1995年 | 4篇 |
1994年 | 3篇 |
1993年 | 2篇 |
1991年 | 4篇 |
1990年 | 1篇 |
1989年 | 3篇 |
1988年 | 2篇 |
1987年 | 1篇 |
1986年 | 1篇 |
1985年 | 2篇 |
1984年 | 1篇 |
1983年 | 3篇 |
1982年 | 1篇 |
1981年 | 1篇 |
1977年 | 2篇 |
排序方式: 共有135条查询结果,搜索用时 31 毫秒
1.
A total of 54 ovariectomized female guinea pigs were divided into three groups and tested six times at 2-week intervals for their responsiveness to exogenous ovarian hormones (3 days of 4 micrograms/kg estradiol benzoate plus 1 day of 0.4 mg/kg progesterone) or control injections (0.2 ml oil vehicle). Two weeks after ovariectomy, treatment with estradiol significantly reduced food intake and body weight, and also produced vaginal membrane rupture in 98.1% of the females. When tested for sexual behavior at 4, 6, and 8 hr after the progesterone injection, 29 of the subjects (53.7%) displayed lordosis in response to manual stimulation. Twelve weeks after ovariectomy, the effects of estradiol on food intake, body weight, and vaginal membrane condition had not diminished. However, the overall proportion of females from which lordosis could be elicited declined to 27.8%. Biweekly injections of estradiol benzoate plus progesterone to one of the groups of females did not prevent this decline in the sexual response. Based on these results, it was concluded that the observed reduction in behavioral lordosis does not represent a general decline in the responsiveness of ovariectomized guinea pigs to estrogenic stimulation, but may involve changes in their responsiveness to progesterone or in other mechanisms more specifically associated with sexual behavior. 相似文献
2.
DNA sequences were determined for three to five alleles of the bride-of-
sevenless (boss) gene in each of four species of Drosophila. The product of
boss is a transmembrane receptor for a ligand coded by the sevenless gene
that triggers differentiation of the R7 photoreceptor cell in the compound
eye. Population parameters affecting the rate and pattern of molecular
evolution of boss were estimated from the multinomial configurations of
nucleotide polymorphisms of synonymous codons. The time of divergence
between D. melanogaster and D. simulans was estimated as approximately 1
Myr, that between D. teissieri and D. yakuba as approximately 0.75 Myr, and
that between the two pairs of sibling species as approximately 2 Myr. (The
boss genes themselves have estimated divergence times approximately 50%
greater than the species divergence times.) The effective size of the
species was estimated as approximately 5 x 10(6), and the average mutation
rate was estimated as 1-2 x 10(-9)/nucleotide/generation. The ratio of
amino acid polymorphisms within species to fixed differences between
species suggests that approximately 25% of all possible single-step amino
acid replacements in the boss gene product may be selectively neutral or
nearly neutral. The data also imply that random genetic drift has been
responsible for virtually all of the observed differences in the portion of
the boss gene analyzed among the four species.
相似文献
3.
The contractile basis of amoeboid movement: V. The control of gelation, solation, and contraction in extracts from dictyostelium discoideum 总被引:29,自引:22,他引:7
下载免费PDF全文
![点击此处可从《The Journal of cell biology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Motile extracts have been prepared from Dictyostelium discoideum by homogenization and differential centrifugation at 4 degrees C in a stabilization solution (60). These extracts gelled on warming to 25 degrees Celsius and contracted in response to micromolar Ca++ or a pH in excess of 7.0. Optimal gelation occurred in a solution containing 2.5 mM ethylene glycol-bis (β-aminoethyl ether)N,N,N',N'-tetraacetate (EGTA), 2.5 mM piperazine-N-N'-bis [2-ethane sulfonic acid] (PIPES), 1 mM MgC1(2), 1 mM ATP, and 20 mM KCI at ph 7.0 (relaxation solution), while micromolar levels of Ca++ inhibited gelation. Conditions that solated the gel elicited contraction of extracts containing myosin. This was true regardless of whether chemical (micromolar Ca++, pH >7.0, cytochalasin B, elevated concentrations of KCI, MgC1(2), and sucrose) or physical (pressure, mechanical stress, and cold) means were used to induce solation. Myosin was definitely required for contraction. During Ca++-or pH-elicited contraction: (a) actin, myosin, and a 95,000-dalton polypeptide were concentrated in the contracted extract; (b) the gelation activity was recovered in the material sqeezed out the contracting extract;(c) electron microscopy demonstrated that the number of free, recognizable F-actin filaments increased; (d) the actomyosin MgATPase activity was stimulated by 4- to 10-fold. In the absense of myosin the Dictyostelium extract did not contract, while gelation proceeded normally. During solation of the gel in the absense of myosin: (a) electron microscopy demonstrated that the number of free, recognizable F- actin filaments increased; (b) solation-dependent contraction of the extract and the Ca++-stimulated MgATPase activity were reconstituted by adding puried Dictyostelium myosin. Actin purified from the Dictyostelium extract did not gel (at 2 mg/ml), while low concentrations of actin (0.7-2 mg/ml) that contained several contaminating components underwent rapid Ca++ regulated gelation. These results indicated : (a) gelation in Dictyostelium extracts involves a specific Ca++-sensitive interaction between actin and several other components; (b) myosin is an absolute requirement for contraction of the extract; (c) actin-myosin interactions capable of producing force for movement are prevented in the gel, while solation of the gel by either physical or chemical means results in the release of F-actin capable of interaction with myosin and subsequent contraction. The effectiveness of physical agents in producting contraction suggests that the regulation of contraction by the gel is structural in nature. 相似文献
4.
S T Butera V L Perez N J Besansky W C Chan B Y Wu G J Nabel T M Folks 《Journal of cellular biochemistry》1991,45(4):366-373
In this report, we describe a human immunodeficiency virus type-1 (HIV-1)-infected promyelocytic cell line, OM, derived from HL-60 cells. Although the OM cell line was biologically cloned twice, the pattern of HIV-1 expression during culture appeared analogous to a classical acute spreading infection and was inhibited by both azidothymidine and recombinant soluble CD4 treatment. The number of OM cells actually expressing HIV-1 at the beginning of culture was 0%, reached a peak of nearly 100% at 6 weeks, and then fell to less than 10% HIV-1+ cells by 10 weeks. Clonal analysis of the surviving cells verified that stable HIV-1+ OM cells resulted from the spreading infection. Southern analysis confirmed the transmission of HIV-1 through these OM cultures and the occurrence of stable clones which resulted. The initial percentage of OM cells actually harboring the HIV-1 genome was less than 0.1%, indicating nonfaithful transmission of an unintegrated HIV-1 genome during clonal expansion. These results demonstrate that extrachromosomal HIV-1 DNA can contribute to the spread of HIV-1 infection and give rise to cells which have stably integrated HIV-1 provirus. 相似文献
5.
Glutathione-S-transferase (GST) isoenzymes were purified from cytosolic preparations from kidneys of male and female rats and kidney cortical specimens from 2 male and 1 female human subjects. GST isoenzyme expression was analyzed by SDS-PAGE, measurement of catalytic activities with specific substrates and determination of their subunits by ELISA and Western blotting using specific antibodies. GST from female rat kidneys showed a preponderance of subunits 3 and 4; levels of these isoenzymes were 3-4 times greater in females than in males. Levels of subunits 1 and 2 were 1.5-2 times greater in the male rat kidneys. Additional minor bands at 24 and 22 kD were observed in GST preparations from both male and female rat kidneys while a band at 25.3 kD was observed only in the male rat kidney. These bands did not react with antibodies to GST 1-1, GST 2-2 or GST 3-4. Both male and female human kidney samples contained GST isoenzymes comparable to the near-neutral (25-5 kD) and basic forms (25 kD) of GSTs found in human liver. In addition a 28-kD band was present in GST preparations from both male and female human kidneys. Additional bands at 29 and 25.2 kD were present only in male human kidneys. Both the kidney cytosol and the total GSTs prepared from female rats shared 2- to 4-fold greater activity with 1,2-dichloro-4-nitrobenzene, ethacrynic acid and trans-4-phenyl-3-buten-2-one than those from males. The measurement of specific subunit amounts by ELISA were in agreement with these results.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
6.
V KW Wong T Li B YK Law E DL Ma N C Yip F Michelangeli C KM Law M M Zhang K YC Lam P L Chan L Liu 《Cell death & disease》2013,4(7):e720
Autophagy is an important cellular process that controls cells in a normal homeostatic state by recycling nutrients to maintain cellular energy levels for cell survival via the turnover of proteins and damaged organelles. However, persistent activation of autophagy can lead to excessive depletion of cellular organelles and essential proteins, leading to caspase-independent autophagic cell death. As such, inducing cell death through this autophagic mechanism could be an alternative approach to the treatment of cancers. Recently, we have identified a novel autophagic inducer, saikosaponin-d (Ssd), from a medicinal plant that induces autophagy in various types of cancer cells through the formation of autophagosomes as measured by GFP-LC3 puncta formation. By computational virtual docking analysis, biochemical assays and advanced live-cell imaging techniques, Ssd was shown to increase cytosolic calcium level via direct inhibition of sarcoplasmic/endoplasmic reticulum Ca2+ ATPase pump, leading to autophagy induction through the activation of the Ca2+/calmodulin-dependent kinase kinase–AMP-activated protein kinase–mammalian target of rapamycin pathway. In addition, Ssd treatment causes the disruption of calcium homeostasis, which induces endoplasmic reticulum stress as well as the unfolded protein responses pathway. Ssd also proved to be a potent cytotoxic agent in apoptosis-defective or apoptosis-resistant mouse embryonic fibroblast cells, which either lack caspases 3, 7 or 8 or had the Bax-Bak double knockout. These results provide a detailed understanding of the mechanism of action of Ssd, as a novel autophagic inducer, which has the potential of being developed into an anti-cancer agent for targeting apoptosis-resistant cancer cells. 相似文献
7.
Kurnick JT Ramirez-Montagut T Boyle LA Andrews DM Pandolfi F Durda PJ Butera D Dunn IS Benson EM Gobin SJ van den Elsen PJ 《Journal of immunology (Baltimore, Md. : 1950)》2001,167(3):1204-1211
We have observed that malignant melanoma cells produce a soluble protein factor(s), which down-regulates melanocyte lineage Melan-A/MART-1 Ag expression by melanoma cells with concomitant loss of recognition by Melan-A/MART-1-specific T cells. This down-modulation of Melan-A/MART-1 expression, which we refer to as "Ag silencing," is mediated via its minimal promoter, whereas the promoter for the restricting Ag-presenting HLA-A2 molecule is not affected. Significantly, this Ag silencing is reversible, as removal of factor-containing supernatants from Melan-A/MART-1-expressing cells results in up-regulation of the promoter for the gene encoding this Ag, and renewed expression of the protein. We have evaluated over 20 known factors, none of which accounts for the Ag-silencing activity of the melanoma cell culture supernatants. The existence of this autocrine pathway provides an additional novel explanation for melanoma tumor progression in vivo in the presence of CTL specific for this melanocyte lineage Ag. These observations may have important implications for Melan-A/MART-1-specific CTL-mediated immunotherapy of melanoma tumors. 相似文献
8.
Drago M Chessa M Gianfranco B Bossone E Carminati M 《International journal of cardiovascular interventions》2004,6(3-4):156-159
We describe a case of a congenital coronary artery fistula of the right coronary artery draining into the left atrium in an eight-year-old boy. The initial diagnosis was made after the detection of a continuous cardiac murmur at the age of six years. Transthoracic echocardiography showed the right coronaric ostium dilatation, the site of drainage in the left atrium and left ventricle volume overload. Catheterization confirmed the diagnosis. The patient underwent percutaneous closure by PDA occluder device. Immediate post-closure angiograms showed complete occlusion of the fistula. The patient showed transient ischemic changes on ECG associated to an increase of plasmatic levels of the cardiac enzyme. ECG and cardiac enzyme were normal one week after the procedure. 相似文献
9.
Tesoriere L D'Arpa D Butera D Allegra M Renda D Maggio A Bongiorno A Livrea MA 《Free radical research》2001,34(5):529-540
Fifteen beta-thalassemia intermedia patients, not requiring chronic transfusional therapy, were monitored in order to check their antioxidant status, and the lipid oxidation products in plasma, LDL, and erythrocytes before and during a 9-month oral treatment with 600 mg/day vitamin E. The low level of vitamin E, and high level of malondialdehyde in plasma clearly tended to normalize after three months (P < .001), and were quite similar to control after six months. The abnormally low level of vitamin E in LDL and the four times higher than control basal level of conjugated dienes (LDL-CD), were not modified after three months of treatment. Significant changes of LDL-VE (P < .05) and of the basal LDL-CD (P < .001) were evident after six months. LDL-VE was within the normal range after nine months, whereas LDL-CD still appeared twice as higher than control. Plasma vitamin A, ascorbate, beta-carotene, and lycopene increased markedly at the end of the trial (P < .005). The level of vitamin E in red blood cells was normalized after six months of supplementation. A decrease of the baseline value of conjugated dienes was observed after nine months, although it remained 1.4-fold higher than control. The RBC count and hematocrit appeared higher at the end of the trial (P < .05 and P < .001, respectively). The hemoglobin value did not show variations. A shift to normal of the resistance of erythrocytes to osmotic lysis was observed. Our findings provide evidence that an oral treatment with vitamin E improves the antioxidant/oxidant balance in plasma, LDL particles, and red blood cells, and counteracts lipid peroxidation processes in beta-thalassemia intermedia patients. 相似文献
10.
This paper demonstrates that miscible blends from water-insoluble polymers, such as poly(2,4,4-trimethylhexamethylene terephthalamide) (1), methylamine imidized poly(methyl methacrylate) (2), and aromatic poly(ether sulfone) (3) and water-soluble polymers, such as poly(2-ethyl-2-oxazoline) (4) and poly(N-vinyl pyrrolidone) (5), respectively, represent a new class of supramolecular hydrogels. When the degree of polymerization (DP) of the water-soluble polymer is larger than that of water-insoluble polymer, the resulting hydrogels adsorb extremely high amounts of water (i.e., 229 wt % in the case of the hydrogel 1/4) and remain mechanically tough. The high water uptake capability of these blends is explained by a supramolecular network structure generated by H-bonding and/or other noncovalent interactions between the water-insoluble hydrophobic polymer and water-soluble hydrophilic segments as reversible cross-linking points interconnected by hydrophilic water soluble segments. The glass transition temperatures of these hydrogels are tailored via the ratio between the weight percent of the two polymers and by the glass transition temperature of the parent polymers. These supramolecular hydrogels can be processed from melt or solution and maintain excellent mechanical properties both in dry and in the water swollen state. This class of hydrogels is of interest for areas such as membranes, contact lenses, tissue engineering, and other biomedical applications. 相似文献