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101.
Muhl L Nykjaer A Wygrecka M Monard D Preissner KT Kanse SM 《The Biochemical journal》2007,404(2):191-196
FSAP (Factor VII-activating protease) can inhibit neointima formation and VSMC (vascular smooth-muscle cell) proliferation by cleavage of PDGF-BB (platelet-derived growth factor-BB). Negatively charged polyanions lead to autoactivation of the FSAP, but no information is available concerning the potential regulation of FSAP activity and its metabolism in the vessel wall. In the present study, we demonstrate that the enzymatic activity of FSAP can be inhibited by the serine protease inhibitor, PN-1 (protease nexin-1), that is found in the vasculature. This leads to the loss of the inhibitory effect of FSAP on PDGF-BB-mediated DNA synthesis and mitogen-activated protein kinase phosphorylation in VSMCs. The FSAP-PN-1 complexes bind to the LRP (low-density lipoprotein receptor-related protein) and are subsequently internalized. This binding is inhibited by receptor-associated protein, an antagonist of LRP, as well as heparin. While PDGFbetaR (PDGFbeta receptor) is internalized by an LRP-dependent mechanism after stimulation of cells by PDGF-BB, the FSAP-PN-1 complex neither influenced PDGF-BB-mediated phosphorylation of PDGFbetaR nor its internalization via LRP. Hence, PN-1 inhibits the enzymatic activity of FSAP and neutralizes its effect on PDGF-BB-mediated VSMC proliferation. The FSAP-inhibitor complexes are internalized via LRP without influencing the PDGF-BB signal transduction pathway. 相似文献
102.
Traverso EE Cho MS Wu CF Sater AK Larabell CA Kloc M Etkin LD 《Differentiation; research in biological diversity》2007,75(10):947-956
Abstract The Xenopus laevis tumorhead (TH) protein, a positive regulator of cell proliferation during embryogenesis, shuttles from the cell periphery into the nucleus during embryogenesis. In these studies, we performed a detailed analysis of TH's subcellular localization pattern to characterize its dynamic behavior. We found that TH exhibits distinct patterns of localization in different germ layers. At the blastula stage, TH is present in the apical cell periphery of prospective mesodermal and ectodermal cells. At the gastrula stage, TH is distributed throughout the entire cytoplasm of prospective mesodermal and ectodermal cells, whereas it shows nuclear localization in presumptive endodermal cells. TH moves into the nucleus of mesodermal and ectodermal cells during the neurula and early tailbud stages. To understand if TH is regulated by changes in its subcellular localization, we used a TH mutant containing signals for farnesylation and palmitoylation to tether the protein to the plasma membrane. Ubiquitous overexpression of this mutant causes embryonic lethality at the early gastrula transition. Further examination using TUNEL assays indicated that wild-type TH overexpression induces apoptosis during gastrulation, and that this effect is exacerbated by the overexpression of the membrane-bound TH mutant. Taken together, our results suggest that changes in the sub-cellular localization of the TH protein are important for its function because blocking the nuclear translocation of overexpressed TH increases apoptosis and causes embryos to die. Our data also suggest that TH plays a role outside the nucleus when it is present at the cell periphery. 相似文献
103.
Serious doubts over “Eggs forever?” 总被引:1,自引:0,他引:1
Skaznik-Wikiel M Tilly JC Lee HJ Niikura Y Kaneko-Tarui T Johnson J Tilly JL 《Differentiation; research in biological diversity》2007,75(2):93-99
A recent commentary in this journal by Byskov et al. (2005) claims that, despite published results from numerous independent lines of investigation from our laboratory and others, there does not "exist any evidence for neo-folliculogenesis in the adult mammalian ovary." While we agree with Byskov et al. that our work represents a radical departure from the age-old dogma that mammalian females permanently lose the capacity for oocyte and follicle production during the perinatal period, careful examination of all of the available data leaves no doubt that adult female mammals retain the capacity for oogenesis and folliculogenesis. These findings do not change the fact that exhaustion of the oocyte pool occurs with advancing chronological age--a process responsible for driving the menopause in women--but rather question the basic mechanism underlying age-related ovarian failure. In this regard, studies of aging male mice have demonstrated that testicular atrophy is associated with a dramatic decline in the number, activity and quality of germline stem cells that maintain spermatogenesis during adulthood (Zhang et al., 2006). Therefore, to the contrary of the opinion of Byskov et al. that such a process would be "considered exceptional among stem cells," it is certainly reasonable to hypothesize that a similar deterioration of female germline stem cell function underlies the decline in oocyte quality and the onset of ovarian failure in aging females. Further, while we accept that a departure from conventional thinking can take years to gain widespread acceptance, we feel this resistance to change should not be construed as the sole means to voice opinions about the validity of our data or the maturity of our principal conclusion. 相似文献
104.
Song HW Cauffman K Chan AP Zhou Y King ML Etkin LD Kloc M 《Differentiation; research in biological diversity》2007,75(6):519-528
The early development of metazoans is mainly regulated by differential translation and localization of maternal mRNAs in the embryo. In general, these processes are orchestrated by RNA-binding proteins interacting with specific sequence motifs in the 3'-untranslated region (UTR) of their target RNAs. Hermes is an RNA-binding protein, which contains a single RNA recognition motif (RRM) and is found in various vertebrate species from fish to human. In Xenopus laevis, Hermes mRNA and protein are localized in the vegetal region of oocytes. A subpopulation of Hermes protein is concentrated in a specific structure in the vegetal cortex, called the germ plasm (believed to contain determinants of the germ cell fate) where Hermes protein co-localizes with Xcat2 and RINGO/Spy mRNAs. The level of total Hermes protein decreases during maturation. The precocious depletion of Hermes protein by injection of Hermes antisense morpholino oligonucleotide (HE-MO) accelerates the process of maturation and results in cleavage defects in vegetal blastomeres of the embryo. It is known that several maternal mRNAs including RINGO/Spy and Mos are regulated at the translational level during meiotic maturation and early cleavage in Xenopus. The ectopic expression of RINGO/Spy or Mos causes resumption of meiotic maturation and cleavage arrests, which resemble the loss of Hermes phenotypes. We found that the injection of HE-MO enhances the acceleration of maturation caused by the injection of RINGO/Spy mRNA, and that Hermes protein is present as mRNP complex containing RINGO/Spy, Mos, and Xcat2 mRNAs in vivo. We propose that as an RNA-binding protein, Hermes may be involved in maturation, cleavage events at the vegetal pole and germ cell development by negatively regulating the expression of RINGO/Spy, Mos, and Xcat2 mRNAs. 相似文献
105.
106.
The pleiotropic effects of creatine (Cr) are based mostly on the functions of the enzyme creatine kinase (CK) and its high-energy
product phosphocreatine (PCr). Multidisciplinary studies have established molecular, cellular, organ and somatic functions
of the CK/PCr system, in particular for cells and tissues with high and intermittent energy fluctuations. These studies include
tissue-specific expression and subcellular localization of CK isoforms, high-resolution molecular structures and structure–function
relationships, transgenic CK abrogation and reverse genetic approaches. Three energy-related physiological principles emerge,
namely that the CK/PCr systems functions as (a) an immediately available temporal energy buffer, (b) a spatial energy buffer
or intracellular energy transport system (the CK/PCr energy shuttle or circuit) and (c) a metabolic regulator. The CK/PCr
energy shuttle connects sites of ATP production (glycolysis and mitochondrial oxidative phosphorylation) with subcellular
sites of ATP utilization (ATPases). Thus, diffusion limitations of ADP and ATP are overcome by PCr/Cr shuttling, as most clearly
seen in polar cells such as spermatozoa, retina photoreceptor cells and sensory hair bundles of the inner ear. The CK/PCr
system relies on the close exchange of substrates and products between CK isoforms and ATP-generating or -consuming processes.
Mitochondrial CK in the mitochondrial outer compartment, for example, is tightly coupled to ATP export via adenine nucleotide
transporter or carrier (ANT) and thus ATP-synthesis and respiratory chain activity, releasing PCr into the cytosol. This coupling
also reduces formation of reactive oxygen species (ROS) and inhibits mitochondrial permeability transition, an early event
in apoptosis. Cr itself may also act as a direct and/or indirect anti-oxidant, while PCr can interact with and protect cellular
membranes. Collectively, these factors may well explain the beneficial effects of Cr supplementation. The stimulating effects
of Cr for muscle and bone growth and maintenance, and especially in neuroprotection, are now recognized and the first clinical
studies are underway. Novel socio-economically relevant applications of Cr supplementation are emerging, e.g. for senior people,
intensive care units and dialysis patients, who are notoriously Cr-depleted. Also, Cr will likely be beneficial for the healthy
development of premature infants, who after separation from the placenta depend on external Cr. Cr supplementation of pregnant
and lactating women, as well as of babies and infants are likely to be of benefit for child development. Last but not least,
Cr harbours a global ecological potential as an additive for animal feed, replacing meat- and fish meal for animal (poultry
and swine) and fish aqua farming. This may help to alleviate human starvation and at the same time prevent over-fishing of
oceans. 相似文献
107.
Satoh M Krzyszczak ME Li Y Ceribelli A Ross SJ Chan EK Segal MS Bubb MR Sobel ES Reeves WH 《Arthritis research & therapy》2011,13(3):R73
Introduction
The presence of anti-topoisomerase I (topo I) antibodies is a classic scleroderma (SSc) marker presumably associated with a unique clinical subset. Here the clinical association of anti-topo I was reevaluated in unselected patients seen in a rheumatology clinic setting. 相似文献108.
Miller M Dreisbach A Otto A Becher D Bernhardt J Hecker M Peppelenbosch MP van Dijl JM 《Journal of proteome research》2011,10(9):4018-4032
Staphylococcus aureus is a dangerous opportunistic human pathogen that causes serious invasive diseases when it reaches the bloodstream. Recent studies have shown that S. aureus is highly resistant to killing by professional phagocytes and that such cells even provide a favorable environment for intracellular survival of S. aureus. Importantly, the reciprocal interactions between phagocytes and S. aureus have remained largely elusive. Here we have employed kinase profiling to define the nature and time resolution of the human THP-1 macrophage response toward S. aureus and proteomics to identify the response of S. aureus toward macrophages. The results of these studies reveal major macrophage signaling pathways triggered by S. aureus and proteomic signatures of the responses of S. aureus to macrophages. We also identify human proteins bound to S. aureus that have potential roles in bacterial killing and internalization. Most noticeably, our observations challenge the classical concept that macrophage responses are mainly mediated through Toll-like receptor 2 and NF-κB signaling and highlight the important role of the stress-activated MAP kinase signaling in orchestrating the host defense. 相似文献
109.
Malgorzata Monika Stanczyk 《Reports of Practical Oncology and Radiotherapy》2011,16(5):170-172
The purpose of this paper is to show some aspects of music therapy application in cancer care and to present the integration of music therapy program into a continuous supportive cancer care for inpatients. A cancer diagnosis is one of the most feared and serious life events that causes stress in individuals and families. Cancer disrupts social, physical and emotional well-being and results in a range of emotions, including anger, fear, sadness, guilt, embarrassment and shame. Music therapy is a part of a complementary medicine program in supportive cancer care which accompanies medical treatment. There are many benefits of music therapy for cancer patients—interactive music therapy techniques (instrumental improvisation, singing) as well as receptive music therapy techniques (listening to recorded or live music, music and imaginary) can be used to improve mood, decrease stress, pain, anxiety level and enhance relaxation. Music therapy is an effective form of supporting cancer care for patients during the treatment process. It may be also basic for planning effective programs of rehabilitation to promote wellness, improve physical and emotional well-being and the quality of life. 相似文献
110.
Olszowy P Szultka M Nowaczyk J Buszewski B 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2011,879(25):2542-2548
The polypyrrole (PPy) and polythiophene (PTh) solid phase microextraction (SPME) coatings were obtained with the use of the electropolymerisation and linear sweep voltammetry. Such fibers were modified by an ozone treatment in a gaseous phase in the concentration of 2.1 ± 0.2 × 10(-5) mol dm(-3). Both kinds of fibers were applied in the microextraction of linezolid from standard solutions to compare the extraction efficiencies displayed by these sorption phases. In these investigations a better adsorption capacity was obtained for polypyrrole fibers and hence only these kinds of fibers were utilized in the measurements from human plasma. In all measurements the concentrations of the drugs were in the range from 1 to 20 μg ml(-1) (standard solutions) and 1 to 15 μg ml(-1) (human plasma). Before the measurements, an optimization of the desorption solution experiments was performed. The correlation coefficients (R) obtained in the standard solution and human plasma were in the range from 0.8399 to 0.9970. The relative standard deviations (RSDs) were in the range of 0.1-7.6%. 相似文献