全文获取类型
收费全文 | 5263篇 |
免费 | 424篇 |
国内免费 | 2篇 |
专业分类
5689篇 |
出版年
2023年 | 26篇 |
2022年 | 42篇 |
2021年 | 90篇 |
2020年 | 53篇 |
2019年 | 74篇 |
2018年 | 85篇 |
2017年 | 77篇 |
2016年 | 145篇 |
2015年 | 272篇 |
2014年 | 278篇 |
2013年 | 286篇 |
2012年 | 462篇 |
2011年 | 412篇 |
2010年 | 274篇 |
2009年 | 239篇 |
2008年 | 321篇 |
2007年 | 315篇 |
2006年 | 297篇 |
2005年 | 286篇 |
2004年 | 269篇 |
2003年 | 263篇 |
2002年 | 245篇 |
2001年 | 58篇 |
2000年 | 36篇 |
1999年 | 76篇 |
1998年 | 73篇 |
1997年 | 45篇 |
1996年 | 42篇 |
1995年 | 47篇 |
1994年 | 54篇 |
1993年 | 35篇 |
1992年 | 41篇 |
1991年 | 34篇 |
1990年 | 28篇 |
1989年 | 37篇 |
1988年 | 23篇 |
1987年 | 30篇 |
1986年 | 16篇 |
1985年 | 20篇 |
1984年 | 19篇 |
1983年 | 27篇 |
1982年 | 17篇 |
1981年 | 10篇 |
1980年 | 11篇 |
1979年 | 24篇 |
1977年 | 11篇 |
1976年 | 7篇 |
1975年 | 9篇 |
1974年 | 8篇 |
1973年 | 7篇 |
排序方式: 共有5689条查询结果,搜索用时 0 毫秒
991.
992.
The case for Survivin as mitotic regulator 总被引:13,自引:0,他引:13
Survivin has been proposed to inhibit apoptosis and to regulate cell division. However, controversy still exists as to whether Survivin can indeed execute these distinct functions and if Survivin somehow coordinates apoptosis and (abnormal) cell division. Recent evidence has demonstrated that Survivin acts as a subunit of the chromosomal passenger complex, which is essential for proper chromosome segregation and cytokinesis. Within this complex, the mitotic kinase Aurora B acts as the enzymatic core, whereas Survivin dictates chromosomal passenger complex localization. This function of Survivin appears to be conserved throughout evolution. Although these findings do not exclude a role for Survivin as apoptosis inhibitor, they make a very strong case for Survivin as mitotic regulator. 相似文献
993.
Wållberg A Nilsson K Osterlund K Peterson A Elg S Raboisson P Bauer U Hammerland LG Mattsson JP 《Bioorganic & medicinal chemistry letters》2006,16(5):1142-1145
Fenobam (1) was developed by McNeil Laboratories as an anxiolytic agent with an unknown molecular target in the late 1970s. In a recent publication, it was revealed that fenobam is a non-competitive mGluR5 antagonist. Herein, we present the structure-activity relationship of fenobam and its analogues and similarities between the SAR of mGluR5 antagonism and the SAR of CNS properties originally reported by McNeil are discussed. 相似文献
994.
Snedeker JG Walz FH Muser MH Schroeder G Mueller TL Müller R 《Journal of biomechanics》2006,39(14):2709-2713
Pelvic and femoral neck bone surface strains were recorded in five full-body human cadaver vehicle-pedestrian impacts. Impacts were performed at 40 km/h using automotive front ends constructed to represent those used in previously reported finite element simulations. While experimental kinematics and bone strains closely matched model predictions, observed pelvic fractures did not consistently agree with the model, and could not be solely explained by vehicle geometry. In an attempt to reconcile injury outcome with factors apart from vehicle design, a proxy measure of subject skeletal health was assessed by high-resolution quantitative computed tomography (HRqCT) of the femoral neck. The incidence of hip/pelvis fracture was found to be consistent with low volumetric bone mineral density and low trabecular bone density. This finding lends quantitative support to the notion that healthy trabecular architecture is crucial in withstanding non-physiological impact loads. Furthermore, it is recommended that injury criteria used to assess vehicle safety with regard to pedestrians consider the increased susceptibility of elderly victims to pelvic fracture. 相似文献
995.
Baum P Schmid R Ittrich C Rust W Fundel-Clemens K Siewert S Baur M Mara L Gruenbaum L Heckel A Eils R Kontermann RE Roth GJ Gantner F Schnapp A Park JE Weith A Quast K Mennerich D 《PloS one》2010,5(12):e14272
A phenocopy is defined as an environmentally induced phenotype of one individual which is identical to the genotype-determined phenotype of another individual. The phenocopy phenomenon has been translated to the drug discovery process as phenotypes produced by the treatment of biological systems with new chemical entities (NCE) may resemble environmentally induced phenotypic modifications. Various new chemical entities exerting inhibition of the kinase activity of Transforming Growth Factor β Receptor I (TGF-βR1) were qualified by high-throughput RNA expression profiling. This chemical genomics approach resulted in a precise time-dependent insight to the TGF-β biology and allowed furthermore a comprehensive analysis of each NCE's off-target effects. The evaluation of off-target effects by the phenocopy approach allows a more accurate and integrated view on optimized compounds, supplementing classical biological evaluation parameters such as potency and selectivity. It has therefore the potential to become a novel method for ranking compounds during various drug discovery phases. 相似文献
996.
Kassmann CM Quintes S Rietdorf J Möbius W Sereda MW Nientiedt T Saher G Baes M Nave KA 《FEBS letters》2011,585(14):2205-2211
Demyelinating diseases of the nervous system cause axon loss but the underlying mechanisms are not well understood. Here we show by confocal and electron microscopy that in myelin-forming glia peroxisomes are associated with myelin membranes. When peroxisome biogenesis is experimentally perturbed in Pex5 conditional mouse mutants, myelination by Schwann cells appears initially normal. However, in nerves of older mice paranodal loops become physically unstable and develop swellings filled with vesicles and electron-dense material. This novel model of a demyelinating neuropathy demonstrates that peroxisomes serve an important function in the peripheral myelin compartment, required for long-term axonal integrity. 相似文献
997.
Fuchs R Schraml E Leitinger G Letofsky-Papst I Stelzer I Haas HS Schauenstein K Sadjak A 《Experimental cell research》2011,317(20):2969-2980
Even though the erythroleukemia cell lines K562 and HEL do not express α1-adrenoceptors, some α1-adrenergic drugs influence both survival and differentiation of these cell lines. Since Ca2+ is closely related to cellular homeostasis, we examined the capacity of α1-adrenergic drugs to modulate the intracellular Ca2+ content in K562 cells. Because of morphological alterations of mitochondria following α1-adrenergic agonist treatment, we also scrutinized mitochondrial functions. In order to visualize the non-adrenoceptor binding site(s) of α1-adrenergic drugs in erythroleukemia cells, we evaluated the application of the fluorescent α1-adrenergic antagonist BODIPY® FL-Prazosin. We discovered that the α1-adrenergic agonists naphazoline, oxymetazoline and also the α1-adrenergic antagonist benoxathian are able to raise the intracellular Ca2+-content in K562 cells. Furthermore, we demonstrate that naphazoline treatment induces ROS-formation as well as an increase in Δψm in K562 cells. Using BODIPY® FL-Prazosin we were able to visualize the non-adrenoceptor binding site(s) of α1-adrenergic drugs in erythroleukemia cells. Interestingly, the SERCA-inhibitor thapsigargin appears to interfere with the binding of BODIPY® FL-Prazosin.Our data suggest that the effects of α1-adrenergic drugs on erythroleukemia cells are mediated by a thapsigargin sensitive binding site, which controls the fate of erythroleukemia cells towards differentiation, senescence and cell death through modulation of intracellular Ca2+. 相似文献
998.
Herter S Schmidt M Thompson ML Mikolasch A Schauer F 《Applied microbiology and biotechnology》2011,90(3):1037-1049
Laccases are copper-containing phenol oxidases that are commonly found in many types of plant, insect, fungi and bacteria.
Whilst phenol oxidases have been well characterized in fungal species, laccase-type enzymes originating from bacteria have
been much less well defined. Bacteria belonging to the family Azotobacteraceae share many morphological characteristics with
strains already known to exhibit polyphenol and phenol oxidase activity; and hence the aim of this work was to identify and
characterize a novel laccase from the isolated strain Azotobacter chroococcum SBUG 1484 in an attempt to provide further understanding of the roles such enzymes play in physiological development. Laccase
activity was clearly observed through oxidation of 2,6-dimethoxyphenol, other typical substrates including: methoxy-monophenols,
ortho- and para-diphenols, 4-hydroxyindole, and the non-phenolic compound para-phenylenediamine. A. chroococcum SBUG 1484 showed production of a cell-associated phenol oxidase when grown under nitrogen-fixing conditions, and was also
observed when cells enter the melanogenic and encystment stages of growth. Catechol which is structurally related to melanin
compounds was also released from Azotobacter cells into the surrounding culture medium during nitrogen-fixing growth. From our results we propose that a membrane-bound
laccase plays an important role in the formation of melanin, which was monitored to correlate with progression of A. chroococcum SBUG 1484 cells into the encystment stage of growth. 相似文献
999.
Schöpper H Palme R Ruf T Huber S 《Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology》2011,181(8):1089-1100
Stress, when extreme or chronic, can have a negative impact on health and survival of mammals. This is especially true for
females during reproduction when self-maintenance and investment in offspring simultaneously challenge energy turnover. Therefore,
we investigated the effects of repeated stress during early- and mid-gestation on the maternal stress axis, body weight gain
and reproductive output. Female guinea pigs (Cavia aperea f. porcellus, n = 14) were either stressed (treatment: exposure to strobe light in an unfamiliar environment on gestational day -7, 0, 7,
14, 21, 28, 35, 42) or left completely undisturbed (control) throughout pregnancy. Females of both groups received the same
respective diets, and reproductive parameters were evaluated upon parturition. Additionally, hormonal data were obtained from
blood and feces. The stress exposure induced a significant increase in plasma cortisol concentrations during the afternoon.
In contrast to this short-term response in plasma cortisol concentrations, we found no significant differences in the levels
of cortisol metabolites in feces collected after stress exposure between groups and even significantly decreased levels of
fecal cortisol metabolites on non-stress days over time in treatment females. Among treatment females, gain in body weight
was attenuated over gestation and body weight was lower compared to control females during lactation, especially in cases
of large litter sizes. No differences could be seen in the reproductive parameters. We conclude that repeated stress exposure
with strobe light during early- and mid-gestation results in a down-regulation of the hypothalamic–pituitary–adrenal axis
and lower weight gain in treatment females, but has no effect on reproductive output. 相似文献
1000.
Figueiredo CP Antunes VL Moreira EL de Mello N Medeiros R Di Giunta G Lobão-Soares B Linhares M Lin K Mazzuco TL Prediger RD Walz R 《Peptides》2011,32(4):781-789
The glucose-dependent insulinotropic peptide receptor (GIPR) has been implicated with neuroplasticity and may be related to epilepsy. GIPR expression was analyzed by immunohistochemistry in the hippocampus (HIP) and neocortex (Cx) of rats undergoing pilocarpine induced status epilepticus (Pilo-SE), and in three young male patients with left mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE-HS) treated surgically. A combined GIPR immunohistochemistry and Fluoro-Jade staining was carried out to investigate the association between the GIPR expression and neuronal degeneration induced by Pilo-SE. GIPR was expressed in the cytoplasm of neurons from the HIP CA subfields, dentate gyrus (DG) and Cx of animals and human samples. The GIPR expression after the Pilo-SE induction increases significantly in the HIP after 1 h and 5 days, but not after 12 h or 50 days. In the Cx, the GIPR expression increases after 1 h, 12 h and 5 days, but not 50 days after the Pilo-SE. The expression of GIPR 12 h after Pilo-SE was inversely proportional to the Fluoro-Jade staining intensity. In the human tissue, GIPR expression patterns were similar to those observed in chronic Pilo-SE animals. No Fluoro-Jade stained cells were observed in the human sample. GIPR is expressed in human HIP and Cx. There was a time and region dependent increase of GIPR expression in the HIP and Cx after Pilo-SE that was inversely associated to neuronal degeneration. 相似文献