全文获取类型
收费全文 | 1572篇 |
免费 | 81篇 |
专业分类
1653篇 |
出版年
2024年 | 3篇 |
2023年 | 8篇 |
2022年 | 26篇 |
2021年 | 47篇 |
2020年 | 36篇 |
2019年 | 30篇 |
2018年 | 59篇 |
2017年 | 52篇 |
2016年 | 69篇 |
2015年 | 90篇 |
2014年 | 94篇 |
2013年 | 108篇 |
2012年 | 155篇 |
2011年 | 135篇 |
2010年 | 94篇 |
2009年 | 50篇 |
2008年 | 98篇 |
2007年 | 99篇 |
2006年 | 91篇 |
2005年 | 81篇 |
2004年 | 70篇 |
2003年 | 68篇 |
2002年 | 48篇 |
2001年 | 9篇 |
2000年 | 3篇 |
1998年 | 8篇 |
1996年 | 1篇 |
1995年 | 3篇 |
1994年 | 2篇 |
1993年 | 3篇 |
1991年 | 3篇 |
1990年 | 1篇 |
1989年 | 1篇 |
1987年 | 1篇 |
1985年 | 1篇 |
1983年 | 1篇 |
1980年 | 4篇 |
1978年 | 1篇 |
排序方式: 共有1653条查询结果,搜索用时 10 毫秒
161.
Kinesin-1 drives the movement of diverse cargoes, and it has been proposed that specific kinesin light chain (KLC) isoforms target kinesin-1 to these different structures. Here, we test this hypothesis using two in vitro motility assays, which reconstitute the movement of rough endoplasmic reticulum (RER) and vesicles present in a Golgi membrane fraction. We generated GST-tagged fusion proteins of KLC1B and KLC1D that included the tetratricopeptide repeat domain and the variable C-terminus. We find that preincubation of RER with KLC1B inhibits RER motility, whereas KLC1D does not. In contrast, Golgi fraction vesicle movement is inhibited by KLC1D but not KLC1B reagents. Both RER and vesicle movement is inhibited by preincubation with the GST-tagged C-terminal domain of ubiquitous kinesin heavy chain (uKHC), which binds to the N-terminal domain of uKHC and alters its interaction with microtubules. We propose that although the TRR domains are required for cargo binding, it is the variable C-terminal region of KLCs that are vital for targeting kinesin-1 to different cellular structures. 相似文献
162.
Katarzyna Lisowska Marcin Bizukojc Jerzy Dugoski 《Enzyme and microbial technology》2006,39(7):1464-1470
An unstructured model for phenanthrene bioconversion by filamentous fungus Cunnighamella elegans in stirred tank batch bioreactors was proposed. It was observed that the process of phenanthrene bioconversion is strictly associated with exponential growth of biomass. Therefore, a Monod-type, with Contois term, unstructured model could be applied to describe the process mathematically. The inhibition of biomass growth due to high concentrations of phenanthrene present in the medium was taken into account in the form of Yerusalimski's uncompetitive inhibition term. 相似文献
163.
Słuczanowska-Głabowska S Laszczyńska M Głabowski W Wylot M 《Folia histochemica et cytobiologica / Polish Academy of Sciences, Polish Histochemical and Cytochemical Society》2006,44(1):25-30
The effect of hyperprolactinemia on the prostate has not been well investigated. Since androgens play an important role in prostate development, growth and function, the goal of the present study was to estimate the influence of hyperprolactinemia on expression of the androgen receptor (AR) in rat epithelial cells of prostate dorsal lobe and on morphology of these cells. Studies were performed on sexually mature male Wistar rats. The experimental group rats received metoclopramide (MCP) intraperitoneally to provoke hyperprolactinemia. The control group animals were given saline in the same way. For light and electron microscopy the prostate dorsal lobes were obtained routinely. To evaluate the intensity of immunohistochemical reaction for AR in epithelial cells, the optical density was measured and computer-assisted image analysis system was used. Morphological observations of the dorsal lobe epithelial cells were carried out in transmission electron microscope. MCP caused over twofold increase in prolactin (PRL) serum levels. In rats with hyperprolactinemia, the testosterone levels (T) were twofold decreased. The intensity of immunohistochemical reaction for AR in epithelial cells of dorsal lobe in the experimental group was significantly lower than in the control group. In the dorsal lobe epithelial cells of experimental group animals, the transmission electron microscopy (TEM) revealed highly dilated RER cisternae and reduced number of microvilli on the cellular surface when compared to the control group. The results show that hyperprolactinemia in male rats causes morphological abnormalities in the dorsal lobe of prostate. The abnormalities are caused by elevated prolactin either directly or indirectly through decreased level of testosterone. Decreased expression of AR in epithelial cells of prostate dorsal lobe is likely to be caused by decreased testosterone level. 相似文献
164.
The purpose of the present work was to determine if selected fungal strains belonging to wood-rotting Basidiomycetes are able to grow on and to solubilize different insoluble oxides in solid media. Twenty-eight strains of white rot fungi were checked for their growth on oxide-amended media (ZnO, CaO, Cu2O). All strains displayed growth on Zn-amended plates but to a different extent, and Cu2O-amended plates turned out to be the most toxic oxide. Most of the tested strains solubilized oxalates and produced noticeable clear zones under the mycelium. These clear zones were tested for the presence of organic acids, the level of which was clearly elevated upon exposure of fungal strains to insoluble oxides. We determined the presence of oxalic, malic, and formic acids, with oxalic acid the predominant one. 相似文献
165.
Ziolkowska A Rucinski M Pucher A Tortorella C Nussdorfer GG Malendowicz LK 《Chemico-biological interactions》2006,164(3):147-156
Compelling evidence indicates that some endocrine disrupters (EDs), acting as selective estrogen-receptor modulators, interfere with osteoblast differentiation and function. Hence, we investigated whether four EDs [bisphenol-A (BSP), benzophenone-3 (BP3), resveratrol and silymarin] affect differentiation and growth of rat calvarial osteoblast-like (ROB) cells in primary in vitro culture. ROB cells were cultured for up 30 days in a medium supplemented with fetal calf serum (FCS), and conventional RT-PCR detected the expression of collagen-1alpha and osteonectin mRNAs through the entire culture period. Real time-PCR demonstrated that at days 2 and 7 of culture the expressions of collagen-1alpha and osteonectin were very low, and underwent a 192- and a 334-fold increase, respectively, at day 21 of culture. In contrast, osteocalcin expression remained unchanged from days 2 to 21 of culture. EIA showed that ROB cells secreted sizeable amounts of osteocalcin and osteopontin between days 13 and 15 of culture. EDs were added at day 13 of culture at concentrations ranging from 10(-10) to 10(-6) M, being the culture medium deprived of FCS, and their effects were tested 48 h later. None of EDs was found to affect osteocalcin and osteopontin secretion from ROB cells, suggesting that their effects were tested at a relatively earlier stage of culture, when ROB cell differentiation into osteoblats is not fully accomplished, and/or the presence of estrogens contained in FCS is needed for EDs to exert their osteoblast-differentiation modulating action. BSP and BP3, but not resveratrol and silymarin, decreased proliferative activity of cultured ROB cells, a cytotoxic effect conceivably independent of their estrogen-receptor modulating activity. 相似文献
166.
A progressive hydrolysis of phospholipids was observed during the mineralization process mediated by extracellular matrix vesicles. Increasing levels of different hydrolysis products revealed phospholipase A and D activities. The importance of these enzymes for the mineralization process lies in a high rate of hydrolysis of neutral phospholipids and lower rate of degradation of anionic phospholipids, which may favor mineral formation in vesicular membrane and membrane breakdown necessary for the release of mineral deposits into extracellular matrix. In this report, we focus on the phosphorylation-dependent phospholipase D activity during mineral formation initiated by chicken embryo matrix vesicles. 相似文献
167.
Regeneration of the visual chromophore, 11-cis-retinal, is a critical step in restoring photoreceptors to their dark-adapted conditions. This regeneration process, called the retinoid cycle, takes place in the photoreceptor outer segments and the retinal pigment epithelium (RPE). Disabling mutations in nearly all of the retinoid cycle genes are linked to human conditions that cause congenital or progressive defects in vision. Several mouse models with disrupted genes related to this cycle contain abnormal fatty acid retinyl ester levels in the RPE. To investigate the mechanisms of retinyl ester accumulation, we generated single or double knockout mice lacking retinoid cycle genes. All-trans-retinyl esters accumulated in mice lacking RPE65, but they are reduced in double knockout mice also lacking opsin, suggesting a connection between visual pigment regeneration and the retinoid cycle. Only Rdh5-deficient mice accumulate cis-retinyl esters, regardless of the simultaneous disruption of RPE65, opsin, and prRDH. 13-cis-Retinoids are produced at higher levels when the flow of retinoid through the cycle was increased, and these esters are stored in specific structures called retinosomes. Most importantly, retinylamine, a specific and effective inhibitor of the 11-cis-retinol formation, also inhibits the production of 13-cis-retinyl esters. The data presented here support the idea that 13-cis-retinyl esters are formed through an aberrant enzymatic isomerization process. 相似文献
168.
Little is known about the architecture and biochemical composition of the eukaryotic DNA replication fork. To study this problem, we used biotin-streptavidin-modified plasmids to induce sequence-specific replication fork pausing in Xenopus egg extracts. Chromatin immunoprecipitation was employed to identify factors associated with the paused fork. This approach identifies DNA pol alpha, DNA pol delta, DNA pol varepsilon, MCM2-7, Cdc45, GINS, and Mcm10 as components of the vertebrate replisome. In the presence of the DNA polymerase inhibitor aphidicolin, which causes uncoupling of a highly processive DNA helicase from the stalled replisome, only Cdc45, GINS, and MCM2-7 are enriched at the pause site. The data suggest the existence of a large molecular machine, the "unwindosome," which separates DNA strands at the replication fork and contains Cdc45, GINS, and the MCM2-7 holocomplex. 相似文献
169.
Novel gene and gene model detection using a whole genome open reading frame analysis in proteomics 总被引:4,自引:1,他引:3
Fermin D Allen BB Blackwell TW Menon R Adamski M Xu Y Ulintz P Omenn GS States DJ 《Genome biology》2006,7(4):R35-13
Background
Defining the location of genes and the precise nature of gene products remains a fundamental challenge in genome annotation. Interrogating tandem mass spectrometry data using genomic sequence provides an unbiased method to identify novel translation products. A six-frame translation of the entire human genome was used as the query database to search for novel blood proteins in the data from the Human Proteome Organization Plasma Proteome Project. Because this target database is orders of magnitude larger than the databases traditionally employed in tandem mass spectra analysis, careful attention to significance testing is required. Confidence of identification is assessed using our previously described Poisson statistic, which estimates the significance of multi-peptide identifications incorporating the length of the matching sequence, number of spectra searched and size of the target sequence database. 相似文献170.