全文获取类型
收费全文 | 259篇 |
免费 | 27篇 |
出版年
2023年 | 2篇 |
2021年 | 4篇 |
2020年 | 5篇 |
2019年 | 5篇 |
2018年 | 4篇 |
2017年 | 5篇 |
2016年 | 12篇 |
2015年 | 12篇 |
2014年 | 13篇 |
2013年 | 15篇 |
2012年 | 15篇 |
2011年 | 13篇 |
2010年 | 11篇 |
2009年 | 3篇 |
2008年 | 6篇 |
2007年 | 8篇 |
2006年 | 6篇 |
2005年 | 5篇 |
2004年 | 9篇 |
2003年 | 4篇 |
2002年 | 4篇 |
2001年 | 9篇 |
2000年 | 8篇 |
1999年 | 5篇 |
1997年 | 5篇 |
1996年 | 3篇 |
1995年 | 3篇 |
1993年 | 3篇 |
1992年 | 5篇 |
1991年 | 13篇 |
1990年 | 3篇 |
1988年 | 4篇 |
1987年 | 5篇 |
1986年 | 5篇 |
1985年 | 7篇 |
1984年 | 3篇 |
1983年 | 5篇 |
1982年 | 2篇 |
1980年 | 3篇 |
1979年 | 5篇 |
1977年 | 2篇 |
1976年 | 2篇 |
1975年 | 5篇 |
1973年 | 4篇 |
1971年 | 2篇 |
1969年 | 1篇 |
1968年 | 1篇 |
1967年 | 4篇 |
1966年 | 1篇 |
1955年 | 2篇 |
排序方式: 共有286条查询结果,搜索用时 15 毫秒
81.
Elbrønd-Bek H Wellejus A Kelly NM Weidner MS Jørgensen SH 《Neurochemistry international》2011,59(6):821-829
Focusing on development of novel drug candidates for the treatment of neurodegenerative diseases, we developed and synthesized a new compound, 2-(cyclohexylamino)-1-(4-cyclopentylpiperazin-1-yl)-2-methylpropan-1-one (amido-piperizine 1). The compound demonstrated robust neuroprotective properties after both glutamate excitotoxicity and peroxide induced oxidative stress in primary cortical cultures. Furthermore, amido-piperizine 1 was found to significantly induce neurite outgrowth in vitro which could suggest central reparative and regenerative potential of the compound.With these potential beneficial effects in CNS, the ability of the amido-piperizine 1 to penetrate the blood-brain barrier was tested using MDR1-MDCK cells. Amido-piperizine 1 was found not to be a P-gp substrate and to have a high blood-brain barrier penetration potential, indicating excellent availability to the CNS. Moreover, amido-piperizine 1 had a fast metabolic clearance rate in vitro, suggesting that parenteral in vivo administration seems preferable.As an attempt to elucidate a possible mechanism of action, we found that amido-piperizine 1 bound in nano-molar range to the sigma-1 receptor, which could explain the observed neuroprotective and neurotrophic properties, and with a 100-fold lower affinity to the sigma-2 receptor. These results propose that amido-piperizine 1 may hold promise as a drug candidate for the treatment of stroke/traumatic brain injury or other neurodegenerative diseases. 相似文献
82.
Siemeling U Schirrmacher C Glebe U Bruhn C Baio JE Arnadóttir L Castner DG Weidner T 《Inorganica chimica acta》2011,374(1):302-312
Thin metalorganic films were prepared on gold by self-assembly of thioether-functionalised phthalocyaninato complexes from solution. The phthalocyaninato ligands used contain eight peripheral, β-positioned, alkylthio substituents SR (1a: R = n-C8H17, 1b: R = n-C12H25), which serve as headgroups for surface binding and promote lateral assembly, while the disk-like phthalocyaninato core offers the scope for the attachment of axial ligands to the adsorbed molecules. This process was mimicked by coordination of pyridine (Py) to [Zn(1a)] and [Zn(1b)], respectively. The crystal structures of the products [Zn(1a)(Py)] and [Zn(1b)(Py)] were determined. The crystal structures of 4,5-bis(octylthio)phthalodinitrile and 4,5-bis(dodecylthio)phthalodinitrile were also determined. The films fabricated from [Mn(1a)Cl] and [Mn(1b)Cl] on gold were characterised by XPS, ToF-SIMS and NEXAFS spectroscopy, which revealed the presence of well-defined and homogeneous self-assembled monolayers (SAMs), whose constituents are bound to the substrate by thioether-gold linkages. The orientation of the macrocycles is predominantly parallel to the surface. Strong electronic interaction of the manganese(III) centre with the substrate leads to Cl loss upon adsorption and its reduction to MnII. 相似文献
83.
Stanisław Weidner Magdalena Karamać Ryszard Amarowicz Ewa Szypulska Aleksandra Gołgowska 《Acta Physiologiae Plantarum》2007,29(3):283-290
The research focused on the changes of phenolic compounds as well as their antiradical activity and reducing power isolated
from Amur grape (Vitis amurensis) seeds during germination under optimal conditions and under osmotic stress. The seeds were found to contain tannins, (+)
catechin, (−) epicatechin, and gallic acid (in free, ester- and glycoside-bound forms). Extracts from the seeds were also
shown to contain two other phenolic acids: caffeic and p-coumaric acids, in very low levels. During a 3-day seed germination test under osmotic stress (−0.5 MPa), the content of
total phenolics, tannins and phenolic acids declined as compared to the control. However, seed germination under stress conditions
led to a significant increase in the amount of catechins. Because catechin is the one of the units in condensed tannins, its
dynamic increase during seed germination may be involved in metabolism of tannins under osmotic stress. It is also likely
that the synthesis of catechins is greater under stress conditions and these compounds may be engaged in the process of acclimatization
of grapevines to stress conditions. The content of total phenolic compounds in seed extracts is positively correlated with
their antioxidant properties. The extracts from seeds germinated under optimal conditions exhibited strong antiradical properties
against the DPPH (2,2-diphenyl-1-picrylhydrazyl) radical as well as reducing power. As regards the extracts from grape seeds
germinated under osmotic stress, this capability was much weaker. The research demonstrated that antioxidants could interfere
with the oxidation process induced by various stresses by acting as oxygen scavengers, therefore the tolerance to drought
stress might be correlated with an increase in the antioxidant potential. 相似文献
84.
Omisanjo OA Biermann K Hartmann S Heukamp LC Sonnack V Hild A Brehm R Bergmann M Weidner W Steger K 《Histochemistry and cell biology》2007,127(2):175-181
DNA methylation catalyzed by DNA methyltransferases (DNMTs) and histone deacetylation catalyzed by histone deacetylases (HDACs)
play an important role for the regulation of gene expression during carcinogenesis and spermatogenesis. We therefore studied
the cell-specific expression of DNMT1 and HDAC1 for the first time in human testicular cancer and impaired human spermatogenesis.
During normal spermatogenesis, DNMT1 and HDAC1 were colocalized in nuclei of spermatogonia. While HDAC1 was additionally present
in nuclei of Sertoli cells, DNMT1 was restricted to germ cells exhibiting a different expression pattern of mRNA (in pachytene
spermatocytes and round spermatids) and protein (in round spermatids). Interestingly, in infertile patients revealing round
spermatid maturation arrest, round spermatids lack DNMT1 protein, while pachytene spermatocytes became immunopositive for
DNMT1. In contrast, no changes in the expression pattern could be observed for HDAC1. This holds true also in testicular tumors,
where HDAC1 has been demonstrated in embryonal carcinoma, seminoma and teratoma. Interestingly, DNMT1 was not expressed in
seminoma, but upregulated in embryonal carcinoma.
Olufunmilade A. Omisanjo is a scholarship holder of the German Academic Exchange Service (DAAD). Sonja Hartmann is a member
of the German Research Foundation (DFG) Research Training Group 533 Cell–cell-Interaction in Reproduction. 相似文献
85.
Jenny Tigerholm Marcus?E. Petersson Otilia Obreja Esther Eberhardt Barbara Namer Christian Weidner Angelika Lampert Richard?W. Carr Martin Schmelz Erik Fransén 《Biophysical journal》2015,108(5):1057-1071
Following each action potential, C-fiber
nociceptors undergo cyclical changes in excitability, including a period of
superexcitability, before recovering their basal excitability state. The
increase in superexcitability during this recovery cycle depends upon their
immediate firing history of the axon, but also determines the instantaneous
firing frequency that encodes pain intensity. To explore the mechanistic
underpinnings of the recovery cycle phenomenon a biophysical model of a C-fiber
has been developed. The model represents the spatial extent of the axon
including its passive properties as well as ion channels and the Na/K-ATPase ion
pump. Ionic concentrations were represented inside and outside the membrane. The
model was able to replicate the typical transitions in excitability from
subnormal to supernormal observed empirically following a conducted action
potential. In the model, supernormality depended on the degree of conduction
slowing which in turn depends upon the frequency of stimulation, in accordance
with experimental findings. In particular, we show that activity-dependent
conduction slowing is produced by the accumulation of intraaxonal sodium. We
further show that the supernormal phase results from a reduced potassium current
Kdr as a result of accumulation of periaxonal potassium in
concert with a reduced influx of sodium through Nav1.7 relative
to Nav1.8 current. This theoretical prediction was supported by
data from an in vitro preparation of small rat dorsal root ganglion somata
showing a reduction in the magnitude of tetrodotoxin-sensitive relative to
tetrodotoxin -resistant whole cell current. Furthermore, our studies provide
support for the role of depolarization in supernormality, as previously
suggested, but we suggest that the basic mechanism depends on changes in ionic
concentrations inside and outside the axon. The understanding of the mechanisms
underlying repetitive discharges in recovery cycles may provide insight into
mechanisms of spontaneous activity, which recently has been shown to correlate
to a perceived level of pain. 相似文献
86.
Increased residual platelet reactivity remains a burden for coronary artery disease (CAD) patients who received a coronary stent and do not respond sufficiently to treatment with acetylsalicylic acid and clopidogrel. We hypothesized that serotonin antagonism reduces high on-treatment platelet reactivity. Whole blood impedance aggregometry was performed with arachidonic acid (AA, 0.5 mM) and adenosine diphosphate (ADP, 6.5 μM) in addition to different concentrations of serotonin (1-100 μM) in whole blood from 42 CAD patients after coronary stent placement and 10 healthy subjects. Serotonin increased aggregation dose-dependently in CAD patients who responded to clopidogrel treatment: After activation with ADP, aggregation increased from 33.7 ± 1.3% to 40.9 ± 2.0% in the presence of 50 μM serotonin (p<0.05) and to 48.2 ± 2.0% with 100 μM serotonin (p<0.001). The platelet serotonin receptor antagonist ketanserin decreased ADP-induced aggregation significantly in clopidogrel low-responders (from 59.9 ± 3.1% to 37.4 ± 3.5, p<0.01), but not in clopidogrel responders. These results were confirmed with light transmission aggregometry in platelet-rich plasma in a subset of patients. Serotonin hence increased residual platelet reactivity in patients who respond to clopidogrel after coronary stent placement. In clopidogrel low-responders, serotonin receptor antagonism improved platelet inhibition, almost reaching responder levels. This may justify further investigation of triple antiplatelet therapy with anti-serotonergic agents. 相似文献
87.
Axonal regeneration is inhibited by a plethora of different mechanisms in the adult central nervous system (CNS). While neurotrophic factors have been shown to stimulate axonal growth in numerous animal models of nervous system injury, a lack of suitable growth substrates, an insufficient activation of neuron-intrinsic regenerative programs, and extracellular inhibitors of regeneration limit the efficacy of neurotrophic factor delivery for anatomical and functional recovery after spinal cord injury. Thus, growth-stimulating factors will likely have to be combined with other treatment approaches to tap into the full potential of growth factor therapy for axonal regeneration. In addition, the temporal and spatial distribution of growth factors have to be tightly controlled to achieve biologically active concentrations, to allow for the chemotropic guidance of axons, and to prevent adverse effects related to the widespread distribution of neurotrophic factors. Here, we will review the rationale for combinatorial treatments in axonal regeneration and summarize some recent progress in promoting axonal regeneration in the injured CNS using such approaches. 相似文献
88.
DNA damage in blood leukocytes of individuals with sickle cell disease treated with hydroxyurea 总被引:1,自引:0,他引:1
Friedrisch JR Prá D Maluf SW Bittar CM Mergener M Pollo T Kayser M da Silva MA Henriques JA da Rocha Silla LM 《Mutation research》2008,649(1-2):213-220
Hydroxyurea (HU) plays an important role in the treatment of patients with sickle cell disease (SCD). Although HU has been associated with an increased risk of leukemia in some patients with myeloproliferative disorders, the mutagenic and carcinogenic potential of HU has not been established. This study investigated levels of DNA damage using the alkaline (pH>13) comet assay to analyze peripheral blood leukocytes sampled from 28 patients with SCD treated with HU (SCHU) and from 28 normal individuals. The damage index (DI) in the SCHU group was significantly higher than in controls (p<0.05). Gender, smoking or age were not associated with DNA damage in controls or SCHU individuals. In the group of SCHU individuals, mean HU dose and DI were positively correlated, and individuals who received a mean dose of >20 mg/kg HU (DI=24.9+/-5.5) showed significantly more DNA damage than those who received < or =20 mg/kg HU (DI=14.6+/-1.8) (p<0.05). Individuals treated for > or =42 months (DI=23.1+/-4.2) showed significantly greater DNA damage than those treated for <42 months (13.6+/-1.9) (p<0.05). DI was inversely correlated with body mass index in the SCHU group. 相似文献
89.
Dipl.-Psych. Julia Martini Priv.-Doz. Dr. med. habil. Kerstin Weidner Prof. Dr. phil. habil. Jürgen Hoyer 《Psychosomatik und Konsiliarpsychiatrie》2008,2(4):207-215
Anxiety disorders are widespread. In contrast to affective disorders, they are characterized by a high persistence and a low remission rate. A considerable number of women suffer from anxiety disorders not only prior to conception but also throughout the transition into parenthood. The detection of anxiety disorders is complicated by the overlap of somatic and anxiety symptoms. Additionally, certain anxiety syndromes are specifically exacerbated during pregnancy. We present the diagnostic criteria of the most important anxiety disorders and highlight the symptoms that make an adequate diagnosis during pregnancy difficult. We outline the natural course and delineate options for referral and intervention. 相似文献
90.
Tanja A. Grein Felix Schwebel Marco Kress Daniel Loewe Hauke Dieken Denise Salzig Tobias Weidner Peter Czermak 《Biotechnology progress》2017,33(4):989-997
Measles virus (MV) has a natural affinity for cancer cells and oncolytic MV preparations have therefore been investigated in several clinical trials as a potential treatment for cancer. The main bottleneck in the administration of oncolytic MV to cancer patients is the production process, because very large doses of virus particles are required for each treatment. Here, we investigated the productivity of different host cells and found that a high infection efficiency did not necessarily result in high virus yields because virus release is also dependent on the host cell. As well as producing large numbers of active MV particles, host cells must perform well in dynamic cultivation systems. In screening experiments, the highest productivity was achieved by Vero and BJAB cells, but only the Vero cells maintained their high virus productivity when transferred to a stirred tank reactor. We used dielectric spectroscopy as an online monitoring system to control the infection and harvest times, which are known to be critical process parameters. The precise control of these parameters allowed us to achieve higher virus titers with Vero cells in a stirred tank reactor than in a static cultivation system based on T‐flasks, with maximum titers of up to 1011 TCID50 ml?1. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:989–997, 2017 相似文献