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41.
Henrik J Johansson Betzabe C Sanchez Jenny Forshed Olle St?l Helena Fohlin Rolf Lewensohn Per Hall Jonas Bergh Janne Lehti? Barbro K Linderholm 《Clinical proteomics》2015,12(1)
Background
Despite the success of tamoxifen since its introduction, about one-third of patients with estrogen (ER) and/or progesterone receptor (PgR) - positive breast cancer (BC) do not benefit from therapy. Here, we aim to identify molecular mechanisms and protein biomarkers involved in tamoxifen resistance.Results
Using iTRAQ and Immobilized pH gradient-isoelectric focusing (IPG-IEF) mass spectrometry based proteomics we compared tumors from 12 patients with early relapses (<2 years) and 12 responsive to therapy (relapse-free > 7 years). A panel of 13 proteins (TCEAL4, AZGP1, S100A10, ALDH6A1, AHNAK, FBP1, S100A4, HSP90AB1, PDXK, GFPT1, RAB21, MX1, CAPS) from the 3101 identified proteins, potentially separate relapse from non-relapse BC patients. The proteins in the panel are involved in processes such as calcium (Ca2+) signaling, metabolism, epithelial mesenchymal transition (EMT), metastasis and invasion. Validation of the highest expressed proteins in the relapse group identify high tumor levels of CAPS as predictive of tamoxifen response in a patient cohort receiving tamoxifen as only adjuvant therapy.Conclusions
This data implicate CAPS in tamoxifen resistance and as a potential predictive marker.Electronic supplementary material
The online version of this article (doi:10.1186/s12014-015-9080-y) contains supplementary material, which is available to authorized users. 相似文献42.
Myelin protein zero/P0 phosphorylation and function require an adaptor protein linking it to RACK1 and PKC alpha 下载免费PDF全文
Gaboreanu AM Hrstka R Xu W Shy M Kamholz J Lilien J Balsamo J 《The Journal of cell biology》2007,177(4):707-716
Point mutations in the cytoplasmic domain of myelin protein zero (P0; the major myelin protein in the peripheral nervous system) that alter a protein kinase Calpha (PKCalpha) substrate motif (198HRSTK201) or alter serines 199 and/or 204 eliminate P0-mediated adhesion. Mutation in the PKCalpha substrate motif (R198S) also causes a form of inherited peripheral neuropathy (Charcot Marie Tooth disease [CMT] 1B), indicating that PKCalpha-mediated phosphorylation of P0 is important for myelination. We have now identified a 65-kD adaptor protein that links P0 with the receptor for activated C kinase 1 (RACK1). The interaction of p65 with P0 maps to residues 179-197 within the cytoplasmic tail of P0. Mutations or deletions that abolish p65 binding reduce P0 phosphorylation and adhesion, which can be rescued by the substitution of serines 199 and 204 with glutamic acid. A mutation in the p65-binding sequence G184R occurs in two families with CMT, and mutation of this residue results in the loss of both p65 binding and adhesion function. 相似文献
43.
Impacts of nutrient enrichment and sediment on phytoplankton community structure in the northern Baltic Sea 总被引:2,自引:0,他引:2
A three-week mesocosm experiment was conducted in order to study the effects of bottom sediment and nutrient enrichment on
phytoplankton and zooplankton community structure in the Archipelago Sea, northern Baltic Sea. The transparent polyethylene
enclosures included the whole water column and varied in volume from 30 to 40 m3. There were two types of enclosures: some with natural sediment as a bottom and others with a plastic bottom. The experiment
was a 2 × 2 factorial design with presence of sediment and nutrient enrichment as treatment factors. Both the sediment presence
and nutrient enrichment significantly increased water nutrient concentrations and the rate of primary production. However,
external nutrient enrichment and the presence of sediment stimulated the growth of different phytoplankton groups, indicating
that the effect of sediment was not related to nutrient fluxes alone, but involved more complex interactions. External nutrient
enrichment was primarily channelled to picoplanktonic cyanobacteria, the biomass of which increased four- to fivefold due
to enrichment. The presence of sediment increased the biomass of cryptophytes, chrysophytes and prasinophytes, but decreased
the biomass of N2-fixing cyanobacteria. Zooplankton biomass increased during the experiment, but was not affected by the treatments. The study
shows that sediment plays a significant role in phytoplankton dynamics, underlining the importance of including sediment in
shallow-water mesocosm experiments.
Handling editor: J. Padisak 相似文献
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46.
Males Benefit from Mating with Outbred Females in Drosophila littoralis: Male Choice for Female Genetic Quality? 下载免费PDF全文
Outi Ala‐Honkola Lily Laine Nina Pekkala Janne S. Kotiaho Terhi Honkola Mikael Puurtinen 《Ethology : formerly Zeitschrift fur Tierpsychologie》2015,121(6):577-585
The evolution and expression of mate choice behaviour in either sex depends on the sex‐specific combination of mating costs, benefits of choice and constraints on choice. If the benefits of choice are larger for one sex, we would expect that sex to be choosier, assuming that the mating costs and constraints on choice are equal between sexes. Because deliberate inbreeding is a powerful genetic method for experimental manipulation of the quality of study organisms, we tested the effects of both male and female inbreeding on egg and offspring production in Drosophila littoralis. Female inbreeding significantly reduced offspring production (mostly due to lower egg‐to‐adult viability), whereas male inbreeding did not affect offspring production (despite a slight effect of paternal inbreeding on egg‐to‐adult viability). As inbreeding depressed female quality more than male quality, the benefits of mate choice were larger for males than for females. In mate choice experiments, inbreeding did not affect male mating success (measured as a probability to be accepted as a mate in a large group), suggesting that females did not discriminate among inbred and outbred males. In contrast, female mating success was affected by inbreeding, with outbred females having higher mating success than inbred females. This result was not explained by lower activity of inbred females. Our results show that D. littoralis males benefit from mating with outbred females of high genetic quality and suggest adaptive male mate choice for female genetic quality in this species. Thus, patterns of mating success in mate choice trials mirrored the benefits of choice: the sex that benefited more from choice (i.e. males) was more choosy. 相似文献
47.
Sonja Fonfara Domingo Casamian‐Sorrosal Janne Sundermeyer Tanja Rosenberger 《Marine Mammal Science》2015,31(3):998-1013
Heart rate and rhythm is regulated by the autonomic nervous system, which matures during the first months of life. Little is known about heart rate and rhythm development and potential arrhythmias in seal pups during rehabilitation in seal centers. Using an iPhone ECG device, 1 min ECGs were obtained from harbor seal pups admitted to a seal rehabilitation facility. ECGs were taken from 55 seals after admission, 53 seals after 14 d, and 52 seals prior to release. From 24 seal pups additional ECGs were taken daily for the first week of rehabilitation. At admission sinus rhythm with a median heart rate of 148 complexes per minute was detected, prior to release sinus bradycardia or sinus arrhythmia with a median heart rate of 104 complexes minute was present. P wave morphology was highly variable and single supra‐ and ventricular premature complexes were recorded in individual animals. The first 14 d were characterized by highly variable heart rates and rhythms, including episodes of sinus tachycardia and 2nd degree atrioventricular blocks. The reduction in heart rates and development of a regular heart rhythm during rehabilitation suggest adaptation to the unfamiliar environment, resolution of disease, and/or maturation of the autonomic nervous system. 相似文献
48.
Fast and simple detection of pathogens is of utmost importance in health care and the food industry. In this article, a novel technology for the detection of pathogenic bacteria is presented. The technology uses lytic-specific bacteriophages and a nonspecific interaction of cellular components with a luminescent lanthanide chelate. As a proof of principle, Escherichia coli-specific T4 bacteriophage was used to infect the bacteria, and the cell lysis was detected. In the absence of E. coli, luminescent Eu3+–chelate complex cannot be formed and low time-resolved luminescence signal is monitored. In the presence of E. coli, increased luminescence signal is observed as the cellular contents are leached to the surrounding medium. The luminescence signal is observed as a function of the number of bacteria in the sample. The homogeneous assay can detect living E. coli in bacterial cultures and simulated urine samples within 25 min with a detection limit of 1000 or 10,000 bacterial cells/ml in buffer or urine, respectively. The detection limit is at the clinically relevant level, which indicates that the method could also be applicable to clinical settings for fast detection of urine bacteria. 相似文献
49.
Claudia St?ubert Hasanuzzaman Bhuiyan Anna Lindahl Oliver Jay Broom Yafeng Zhu Saiful Islam Sten Linnarsson Janne Lehti? Anders Nordstr?m 《The Journal of biological chemistry》2015,290(13):8348-8359
Cancer cells that escape induction therapy are a major cause of relapse. Understanding metabolic alterations associated with drug resistance opens up unexplored opportunities for the development of new therapeutic strategies. Here, we applied a broad spectrum of technologies including RNA sequencing, global untargeted metabolomics, and stable isotope labeling mass spectrometry to identify metabolic changes in P-glycoprotein overexpressing T-cell acute lymphoblastic leukemia (ALL) cells, which escaped a therapeutically relevant daunorubicin treatment. We show that compared with sensitive ALL cells, resistant leukemia cells possess a fundamentally rewired central metabolism characterized by reduced dependence on glutamine despite a lack of expression of glutamate-ammonia ligase (GLUL), a higher demand for glucose and an altered rate of fatty acid β-oxidation, accompanied by a decreased pantothenic acid uptake capacity. We experimentally validate our findings by selectively targeting components of this metabolic switch, using approved drugs and starvation approaches followed by cell viability analyses in both the ALL cells and in an acute myeloid leukemia (AML) sensitive/resistant cell line pair. We demonstrate how comparative metabolomics and RNA expression profiling of drug-sensitive and -resistant cells expose targetable metabolic changes and potential resistance markers. Our results show that drug resistance is associated with significant metabolic costs in cancer cells, which could be exploited using new therapeutic strategies. 相似文献
50.
Astrid K Stunes Irene Westbroek Björn I Gustafsson Reidar Fossmark Jan H Waarsing Erik F Eriksen Christiane Petzold Janne E Reseland Unni Syversen 《BMC endocrine disorders》2011,11(1):1-13