全文获取类型
收费全文 | 688篇 |
免费 | 51篇 |
国内免费 | 1篇 |
出版年
2022年 | 9篇 |
2021年 | 20篇 |
2020年 | 14篇 |
2019年 | 6篇 |
2018年 | 16篇 |
2017年 | 13篇 |
2016年 | 14篇 |
2015年 | 27篇 |
2014年 | 32篇 |
2013年 | 63篇 |
2012年 | 55篇 |
2011年 | 54篇 |
2010年 | 34篇 |
2009年 | 33篇 |
2008年 | 52篇 |
2007年 | 43篇 |
2006年 | 33篇 |
2005年 | 34篇 |
2004年 | 35篇 |
2003年 | 22篇 |
2002年 | 38篇 |
2001年 | 2篇 |
2000年 | 9篇 |
1999年 | 8篇 |
1998年 | 4篇 |
1995年 | 2篇 |
1994年 | 3篇 |
1993年 | 5篇 |
1992年 | 2篇 |
1991年 | 3篇 |
1990年 | 3篇 |
1989年 | 4篇 |
1988年 | 5篇 |
1987年 | 5篇 |
1985年 | 4篇 |
1984年 | 2篇 |
1983年 | 2篇 |
1981年 | 3篇 |
1976年 | 1篇 |
1975年 | 2篇 |
1973年 | 4篇 |
1972年 | 1篇 |
1971年 | 2篇 |
1970年 | 1篇 |
1969年 | 3篇 |
1967年 | 1篇 |
1966年 | 2篇 |
1962年 | 2篇 |
1960年 | 1篇 |
1958年 | 1篇 |
排序方式: 共有740条查询结果,搜索用时 31 毫秒
111.
Macrophage colony stimulating factor (MCSF) regulates growth, proliferation and differentiation of haematopoietic cell lineages. Many cancers are known to secrete high level of MCSF, which recruit macrophages into the tumour micro-environment, supporting tumour growth. Herein, we report the cloning of MCSF and subsequent generation of U87MG expressing MCSF stable cell line (U87-MCSF). Cytotoxicity of anti-cancer drug 5-fluorouracil (5-FU) was evaluated on both U87MG and U87-MCSF cells. Interestingly, the proliferation of U87-MCSF cells was less (p<0.001) than that of U87MG cells alone, after treatment with 5-FU. Significant decrease in expression levels of cyclin E and A2 quantified by real time PCR analysis corroborated the reduced proliferation of 5-FU treated U87-MCSF cells. However, JC-1 staining did not reveal any apoptosis upon 5-FU treatment. Notch-1 upregulation induced a possible epithelial-mesenchymal transition in U87-MCSF cells, which accounted for an increase in the proportion of CD24high/CD44less cancer stem cells in U87-MCSF cells after 5-FU treatment. The elevated resistance of U87-MCSF cells towards 5-FU was due to the increase in the expressions (10.2 and 6 fold) of ABCB1 and mdm2, respectively. Furthermore, increase in expressions of ABCG1, mdm2 and CD24 was also observed in U87MG cells after prolonged incubation with 5-FU. Our studies provided mechanistic insights into drug resistance of U87MG cells and also described the pivotal role played by MCSF in augmenting the resistance of U87MG cells to 5-FU. 相似文献
112.
Due to their secretive habits, predicting the pattern of spatial distribution of small carnivores has been typically challenging, yet for conservation management it is essential to understand the association between this group of animals and environmental factors. We applied maximum entropy modeling (MaxEnt) to build distribution models and identify environmental predictors including bioclimatic variables, forest and land cover type, topography, vegetation index and anthropogenic variables for six small carnivore species in Mudumalai Tiger Reserve. Species occurrence records were collated from camera-traps and vehicle transects during the years 2010 and 2011. We used the average training gain from forty model runs for each species to select the best set of predictors. The area under the curve (AUC) of the receiver operating characteristic plot (ROC) ranged from 0.81 to 0.93 for the training data and 0.72 to 0.87 for the test data. In habitat models for F. chaus, P. hermaphroditus, and H. smithii “distance to village” and precipitation of the warmest quarter emerged as some of the most important variables. “Distance to village” and aspect were important for V. indica while “distance to village” and precipitation of the coldest quarter were significant for H. vitticollis. “Distance to village”, precipitation of the warmest quarter and land cover were influential variables in the distribution of H. edwardsii. The map of predicted probabilities of occurrence showed potentially suitable habitats accounting for 46 km2 of the reserve for F. chaus, 62 km2 for V. indica, 30 km2 for P. hermaphroditus, 63 km2 for H. vitticollis, 45 km2 for H. smithii and 28 km2 for H. edwardsii. Habitat heterogeneity driven by the east-west climatic gradient was correlated with the spatial distribution of small carnivores. This study exemplifies the usefulness of modeling small carnivore distribution to prioritize and direct conservation planning for habitat specialists in southern India. 相似文献
113.
Neeti Nadda Shruti Setia Vivek Vaish Sankar Nath Sanyal 《Molecular and cellular biochemistry》2013,372(1-2):101-112
This study explored the role of pro- and anti-inflammatory cytokines in dimethyl benz(a)anthracene (DMBA)-induced lung cancer and its subsequent correction with a COX-2 inhibitory NSAID, etoricoxib. A single dose of DMBA (20?mg/kg body weight) in 0.9?% NaCl administered intratracheally was used to induce tumors in the rat lungs in 20?weeks. The study of pro-inflammatory cytokines like IL-1??, TNF-??, and IFN-?? revealed their upregulation by DMBA administration and restoration of their levels toward normal by the treatment with etoricoxib, while the anti-inflammatory cytokine IL-2 was found to be down-regulated with carcinogen administration and corrected with etoricoxib treatment. Apoptosis was studied by mitochondrial Bcl-2/Bax ratio and staining with fluorescent dyes acridine orange/ethidium bromide. The results showed a decreased apoptotic level with DMBA which was corrected with etoricoxib. Also, mitochondrial membrane potential was studied using JC-1 and rhodamine-123, which are membrane permeant fluorescent dyes, and generate information about cells at lower and higher mitochondrial membrane potential (???M). The results showed the presence of maximum number of cells with higher ???M in the DMBA group and their number was considerably lowered in the other three groups. 相似文献
114.
Suvadra Das Partha Roy Rajat Pal Runa Ghosh Auddy Abhay Sankar Chakraborti Arup Mukherjee 《PloS one》2014,9(7)
Silybin, is one imminent therapeutic for drug induced hepatotoxicity, human prostrate adenocarcinoma and other degenerative organ diseases. Recent evidences suggest that silybin influences gluconeogenesis pathways favorably and is beneficial in the treatment of type 1 and type 2 diabetes. The compound however is constrained due to solubility (0.4 mg/mL) and bioavailabilty limitations. Appropriate nanoparticle design for silybin in biocompatible polymers was thus proposed as a probable solution for therapeutic inadequacy. New surface engineered biopolymeric nanoparticles with high silybin encapsulation efficiency of 92.11% and zeta potential of +21 mV were designed. Both the pure compound and the nanoparticles were evaluated in vivo for the first time in experimental diabetic conditions. Animal health recovered substantially and the blood glucose levels came down to near normal values after 28 days treatment schedule with the engineered nanoparticles. Restoration from hyperglycemic damage condition was traced to serum insulin regeneration. Serum insulin recovered from the streptozotocin induced pancreatic damage levels of 0.17±0.01 µg/lit to 0.57±0.11 µg/lit after nanoparticle treatment. Significant reduction in glycated hemoglobin level, and restoration of liver glycogen content were some of the other interesting observations. Engineered silybin nanoparticle assisted recovery in diabetic conditions was reasoned due to improved silybin dissolution, passive transport in nanoscale, and restoration of antioxidant status. 相似文献
115.
116.
During the last two decades, new insights into proteasome function and its role in several human diseases made it a potential therapeutic target. In this context, Amblyomin-X is a Kunitz-type FXa inhibitor similar to endogenous tissue factor pathway inhibitor (TFPI) and is a novel proteasome inhibitor. Herein, we have demonstrated Amblyomin-X cytotoxicity to different tumor cells lines such as pancreatic (Panc1, AsPC1BxPC3) and melanoma (SK-MEL-5 and SK-MEL-28). Of note, Amblyomin-X was not cytotoxic to normal human fibroblast cells. In addition, Amblyomin-X promoted accumulation of ER stress markers (GRP78 and GADD153) in sensitive (SK-MEL-28) and bortezomib-resistant (Mia-PaCa-2) tumor cells. The intracellular calcium concentration [Ca2+] i was slightly modulated in human tumor cells (SK-MEL-28 and Mia-PaCa-2) after 24 h of Amblyomin-X treatment. Furthermore, Amblyomin-X induced mitochondrial dysfunction, cytochrome-c release, PARP cleavage, and activation of caspase cascade in both human tumor (SK-MEL-28 and Mia-PaCa-2) cells. These investigations might help in further understanding of the antitumor properties of Amblyomin-X. 相似文献
117.
118.
Starvation of 48 h old fifth instar larvae depressed storage protein titres initially for 48 h but retained the levels comparable
to control thereafter, possibly due to nutrients obtained during the 48 h feeding after fourth ecdysis. After an initial decline
ligated larvae accumulated maximum storage proteins in haemolymph. This is because of inhibitory juvenile hormone titre at
the basal level besides the appropriate release of 20-hydroxyecdysone from the ectopic source(s). Injection of methoprene
(10 Μg/larva) repressed accumulation of storage proteins while 20-hydroxyecdysone (10 Μg/larva) increased the same. P-soyatose
injection to starved and ligated larvae accelerated storage protein accumulation in haemolymph, signalling nutrient indispensability
for initiation of storage protein synthesis at the appropriate time of last instar development inBombyx mori. 相似文献
119.
It is known that over half of the proteins encoded by most organisms function as oligomeric complexes. Oligomerization confers structural stability and dynamics changes in proteins. We investigate the effects of oligomerization on protein dynamics and its functional significance for a set of 145 multimeric proteins. Using coarse‐grained elastic network models, we inspect the changes in residue fluctuations upon oligomerization and then compare with residue conservation scores to identify the functional significance of these changes. Our study reveals conservation of about ½ of the fluctuations, with ¼ of the residues increasing in their mobilities and ¼ having reduced fluctuations. The residues with dampened fluctuations are evolutionarily more conserved and can serve as orthosteric binding sites, indicating their importance. We also use triosephosphate isomerase as a test case to understand why certain enzymes function only in their oligomeric forms despite the monomer including all required catalytic residues. To this end, we compare the residue communities (groups of residues which are highly correlated in their fluctuations) in the monomeric and dimeric forms of the enzyme. We observe significant changes to the dynamical community architecture of the catalytic core of this enzyme. This relates to its functional mechanism and is seen only in the oligomeric form of the protein, answering why proteins are oligomeric structures. Proteins 2017; 85:1422–1434. © 2017 Wiley Periodicals, Inc. 相似文献
120.
Aniruddha Majumder Qamar Qureshi Kalyanasundaram Sankar Alok Kumar 《European Journal of Wildlife Research》2017,63(1):17
Long-term monitoring of tiger population is essential in any human-dominated landscape as globally their population is showing a declining trend due to unrelenting stress or stochastic events. In view of that, Bengal tiger population was monitored in Pench Tiger Reserve (Pench), Madhya Pradesh of Central India between May 2006 and April 2013. The population, age-sex ratios, survival rate, growth rate, and recruitment pattern of adult (≥36 month), subadult (≥18 to 36 month), and cubs (≤15 month) were studied using camera trap and radio-telemetry techniques. Overall, tiger density ± SE/100 km2 using Maximum Likelihood Spatial Explicit Capture Recapture method was 5.5 ± 1.6 in first trapping period or year and 3.7 ± 0.8 in last or seventh trapping year. The estimated survival rate of all tiger (n = 66) was 0.66 (±0.04), whereas mean annual growth rate (±SE) was 1.15 (±0.11) i.e. 15%. The sex ratio (male/female) found to be female biased and more than 80% of overall recruitment was contributed by female tiger. The dispersal of subadults in the tiger population contributed gradual fluctuation in survival rate and annual growth rate, as resident adult tiger population remained almost stable over the study period. As the overall tigers are surviving in a small population size and operating at carrying capacity, the important corridors connecting with neighboring population of Kanha Tiger Reserve and Satpura Tiger Reserve may ensure constant emigration and immigration to reduce the chances of genetic drift or inbreeding in the Pench tiger population. 相似文献