全文获取类型
收费全文 | 110684篇 |
免费 | 1210篇 |
国内免费 | 906篇 |
专业分类
112800篇 |
出版年
2023年 | 168篇 |
2022年 | 383篇 |
2021年 | 719篇 |
2020年 | 424篇 |
2019年 | 454篇 |
2018年 | 12261篇 |
2017年 | 11035篇 |
2016年 | 8080篇 |
2015年 | 1479篇 |
2014年 | 1434篇 |
2013年 | 1873篇 |
2012年 | 5798篇 |
2011年 | 14092篇 |
2010年 | 12697篇 |
2009年 | 8858篇 |
2008年 | 10542篇 |
2007年 | 12102篇 |
2006年 | 955篇 |
2005年 | 1139篇 |
2004年 | 1465篇 |
2003年 | 1439篇 |
2002年 | 1158篇 |
2001年 | 563篇 |
2000年 | 448篇 |
1999年 | 284篇 |
1998年 | 112篇 |
1997年 | 103篇 |
1996年 | 95篇 |
1995年 | 79篇 |
1994年 | 65篇 |
1993年 | 87篇 |
1992年 | 185篇 |
1991年 | 190篇 |
1990年 | 129篇 |
1989年 | 97篇 |
1988年 | 149篇 |
1987年 | 113篇 |
1986年 | 86篇 |
1985年 | 87篇 |
1984年 | 94篇 |
1983年 | 68篇 |
1982年 | 43篇 |
1981年 | 49篇 |
1980年 | 46篇 |
1979年 | 61篇 |
1978年 | 40篇 |
1977年 | 46篇 |
1975年 | 37篇 |
1972年 | 273篇 |
1971年 | 287篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
161.
Rhamnolipids, produced by Pseudomonas aeruginosa, represent an important group of biosurfactants having various industrial, environmental, and medical applications. Current
methods for rhamnolipid quantification involve the use of strong hazardous acids/chemicals, indirect measurement of the concentration
of sugar moiety, or require the availability of expensive equipment (HPLC-MS). A safer, easier method that measures the whole
rhamnolipid molecules would significantly enhance strain selection, metabolic engineering, and process development for economical
rhamnolipid production. A semi-quantitative method was reported earlier to differentiate between the rhamnolipid-producing
and non-producing strains using agar plates containing methylene blue and cetyl trimethylammonium bromide (CTAB). In this
study, a rapid and simple method for rhamnolipid analysis was developed by systematically investigating the complexation of
rhamnolipids and methylene blue, with and without the presence of CTAB. The method relies on measuring the absorbance (at
638 nm) of the rhamnolipid−methylene blue complex that partitions into the chloroform phase. With P. aeruginosa fermentation samples, the applicability of this method was verified by comparison of the analysis results with those obtained
from the commonly used anthrone reaction technique. 相似文献
162.
163.
The cell cycle of neurons remains suppressed to maintain the state of differentiation and aberrant cell cycle reentry results in loss of neurons, which is a feature in neurodegenerative disorders like Alzheimer''s disease (AD). Present studies revealed that the expression of microRNA 34a (miR-34a) needs to be optimal in neurons, as an aberrant increase or decrease in its expression causes apoptosis. miR-34a keeps the neuronal cell cycle under check by preventing the expression of cyclin D1 and promotes cell cycle arrest. Neurotoxic amyloid β1–42 peptide (Aβ42) treatment of cortical neurons suppressed miR-34a, resulting in unscheduled cell cycle reentry, which resulted in apoptosis. The repression of miR-34a was a result of degradation of TAp73, which was mediated by aberrant activation of the MEK extracellular signal-regulated kinase (ERK) pathway by Aβ42. A significant decrease in miR-34a and TAp73 was observed in the cortex of a transgenic (Tg) mouse model of AD, which correlated well with cell cycle reentry observed in the neurons of these animals. Importantly, the overexpression of TAp73α and miR-34a reversed cell cycle-related neuronal apoptosis (CRNA). These studies provide novel insights into how modulation of neuronal cell cycle machinery may lead to neurodegeneration and may contribute to the understanding of disorders like AD. 相似文献
164.
Vanessa B. Fortes Júlio César Bicca-Marques 《International journal of primatology》2008,29(3):717-722
We located 4 brown howlers (1 adult male, 2 adult females, and 1 juvenile male) showing abnormally lighter pelage in 3 social
groups comprising 5, 6, and 9 individuals in a 20 ha-forest fragment in the State of Rio Grande do Sul, Brazil. Two additional
groups composed only of normally colored individuals also live in the fragment, which is isolated from nearby fragments by
267–1009 m. They were the only brown howlers with abnormal pelage color out of a total of 386 individuals belonging to 67
groups in 21 fragments in the 5876-ha study area. The isolation of the forest fragment, its high howler density (2.2 individuals⁄ha),
and large group size (8.8 ± 2.4 individuals) may decrease the likelihood of successful immigration into the population, leading
to an increased probability of inbreeding that may facilitate the expression of rare alleles. 相似文献
165.
Random network models have been a popular tool for investigating cortical network dynamics. On the scale of roughly a cubic millimeter of cortex, containing about 100,000 neurons, cortical anatomy suggests a more realistic architecture. In this locally connected random network, the connection probability decreases in a Gaussian fashion with the distance between neurons. Here we present three main results from a simulation study of the activity dynamics in such networks. First, for a broad range of parameters these dynamics exhibit a stationary state of asynchronous network activity with irregular single-neuron spiking. This state can be used as a realistic model of ongoing network activity. Parametric dependence of this state and the nature of the network dynamics in other regimes are described. Second, a synchronous excitatory stimulus to a fraction of the neurons results in a strong activity response that easily dominates the network dynamics. And third, due to that activity response an embedding of a divergent-convergent feed-forward subnetwork (as in synfire chains) does not naturally lead to a stable propagation of synchronous activity in the subnetwork; this is in contrast to our earlier findings in isolated subnetworks of that type. Possible mechanisms for stabilizing the interplay of volleys of synchronous spikes and network dynamics by specific learning rules or generalizations of the subnetworks are discussed. 相似文献
166.
A significant macrophage and T-cell infiltrate commonly occurs in inflammatory joint conditions such as rheumatoid arthritis
that have significant bone destruction. Cytokines produced by activated macrophages and T cells are implicated in arthritis
pathogenesis and are involved in osteoclast-mediated bone resorption. The scope of the present review is to analyze current
knowledge and to provide a better understanding of how macrophage-derived factors promote the differentiation of a novel T-helper
subset (Th17) that promotes osteoclast formation and activation. 相似文献
167.
Reelin is an extracellular matrix molecule that is involved in the normal development of the cerebellar lamination, Bergmann glial fibres alignment, Purkinje cell monolayer arrangement and granule cell migration. In this study, we have examined the effects of maternal exposure of deltamethrin (DLT), a type II pyrethroid insecticide, on the structural and functional development of rat cerebellum during postnatal life. DLT (0.75 mg/kg body weight, intraperitoneally dissolved in dimethylsulphoxide) was administered in timed pregnant rats during two different gestational time periods, i.e. gestational days of 7–10 and 11–14, respectively. In DLT exposed rats, a significant overexpression of reelin was observed in the cells of the external granule cell layer (EGL) and internal granule cell layer along with an ectopic expression of reelin in the EGL as well as in the migrating granule cells just below the EGL, revealing an arrest of granule cell migration in this zone. Mis-orientation and hypertrophy of the Bergmann glial fibres further hampered the journey of the granule cells to their final destination. Possibly reelin overexpression also caused misalignment of the Purkinje cells and inhibited the neurite growth leading to a significant decrease in the spine density, main dendritic length and width of the dendritic arbour. Thus, it is proposed that the DLT exerts its neurotoxic effects possibly via the intracellular accumulation and low release of reelin leading to an impaired granule cell and Purkinje cell migration, inhibition of neurite outgrowth and reduced spine density. Such impaired cerebellar development leads to motor coordination deficits. 相似文献
168.
Lucas Spohn Christiane Fichter Martin Werner Silke Lassmann 《Journal of cell communication and signaling》2016,10(1):41-47
Background: The EGF receptor is a therapeutic target in cancer cells, whereby mutations of EGFR and/or signalling members act as predictive markers. EGFR however also exhibits dynamic changes of subcellular localization, leading to STAT5 complex formation, nuclear translocation and induction of Aurora-A expression in squamous cancer cells. We previously described high EGFR and Aurora-A expression in esophageal cancer cells. Here, we investigated subcellular localization of EGFR and STAT5 in esophageal cancer cells. Results: Quantitative immunofluorescence analyses of four esophageal cancer cell lines reflecting esophageal squamous cell carcinomas (ESCC) and esophageal adenocarcinomas (EAC) revealed that the subcellular localization of EGFR was shifted from a membranous to cytoplasmic localization upon EGF-stimulation in OE21 (ESCC) cells. Thereby, EGFR in part co-localized with E-Cadherin. In parallel, phosphorylated STAT5-Tyr694 appeared to increase in the nucleus and to decrease at the cell membrane. In three additional cell lines, EGFR was only marginally (Kyse-410/ESCC; OE19/EAC) and weakly (OE33, EAC) detectable at the cell membrane. Partial co-localization of EGFR and E-Cadherin occurred in OE33 cells. Post EGF-stimulation, EGFR was detected in the cytoplasm, resembling endosomal compartments. Furthermore, OE19 and OE33 exhibited nuclear STAT5-Tyr694 phosphorylation upon EGF-stimulation. None of the four cell lines showed nuclear EGFR expression and localization. Conclusion: In contrast to other (squamous) cancer cells, activation of EGFR in esophageal squamous cancer cells does not result in nuclear translocation of EGFR. Still, the subcellular localization of EGFR may influence STAT5-associated signaling pathways in esophageal cancer cells and hence possibly also the responses to ErbB, respective EGFR-targeted therapies. 相似文献
169.
Four different bacterial isolates obtained from a stable bacterial consortium were capable of utilizing pentachlorophenol
(PCP) as sole carbon and energy source. The consortium was developed by continuous enrichment in the chemostat. The degradation
of PCP by bacterial strain was preceded through an oxidative route as indicated by accumulation of tetrachloro-ρ-hydroquinone
and dichlorohydroquinone as determined by high performance liquid chromatography (HPLC). Among the four isolates, Pseudomonas fluorescens exhibited maximum degradation capability and enzyme production. PCP-monooxygenase enzyme was extracted from culture extract
and fractionated by DEAE-cellulose ion exchange chromatography. The molecular weight of the enzyme, purified from Pseudomonas fluorescens, determined by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and gel filtration chromatography was
found to be 24,000 Da.
Received: 22 July 2002 / Accepted: 23 September 2002 相似文献
170.
Hernández-Hernández A Rincón-Arano H Recillas-Targa F Ortiz R Valdes-Quezada C Echeverría OM Benavente R Vázquez-Nin GH 《Chromosoma》2008,117(1):77-87
The synaptonemal complex (SC) is an evolutionarily conserved structure that mediates synapsis of homologous chromosomes during
meiotic prophase I. Previous studies have established that the chromatin of homologous chromosomes is organized in loops that
are attached to the lateral elements (LEs) of the SC. The characterization of the genomic sequences associated with LEs of
the SC represents an important step toward understanding meiotic chromosome organization and function. To isolate these genomic
sequences, we performed chromatin immunoprecipitation assays in rat spermatocytes using an antibody against SYCP3, a major
structural component of the LEs of the SC. Our results demonstrated the reproducible and exclusive isolation of repeat deoxyribonucleic
acid (DNA) sequences, in particular long interspersed elements, short interspersed elements, long terminal direct repeats,
satellite, and simple repeats. The association of these repeat sequences to the LEs of the SC was confirmed by in situ hybridization
of meiotic nuclei shown by both light and electron microscopy. Signals were also detected over the chromatin surrounding SCs
and in small loops protruding from the lateral elements into the SC central region. We propose that genomic repeat DNA sequences
play a key role in anchoring the chromosome to the protein scaffold of the SC.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献