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81.
Cheryl Carson Pichai Raman Jennifer Tullai Lei Xu Martin Henault Emily Thomas Sarita Yeola Jianmin Lao Mark McPate J. Martin Verkuyl George Marsh Jason Sarber Adam Amaral Scott Bailey Danuta Lubicka Helen Pham Nicolette Miranda Jian Ding Hai-Ming Tang Haisong Ju Pamela Tranter Nan Ji Philipp Krastel Rishi K. Jain Andrew M. Schumacher Joseph J. Loureiro Elizabeth George Giuliano Berellini Nathan T. Ross Simon M. Bushell Gül Erdemli Jonathan M. Solomon 《PloS one》2015,10(6)
Englerin A is a structurally unique natural product reported to selectively inhibit growth of renal cell carcinoma cell lines. A large scale phenotypic cell profiling experiment (CLiP) of englerin A on ¬over 500 well characterized cancer cell lines showed that englerin A inhibits growth of a subset of tumor cell lines from many lineages, not just renal cell carcinomas. Expression of the TRPC4 cation channel was the cell line feature that best correlated with sensitivity to englerin A, suggesting the hypothesis that TRPC4 is the efficacy target for englerin A. Genetic experiments demonstrate that TRPC4 expression is both necessary and sufficient for englerin A induced growth inhibition. Englerin A induces calcium influx and membrane depolarization in cells expressing high levels of TRPC4 or its close ortholog TRPC5. Electrophysiology experiments confirmed that englerin A is a TRPC4 agonist. Both the englerin A induced current and the englerin A induced growth inhibition can be blocked by the TRPC4/C5 inhibitor ML204. These experiments confirm that activation of TRPC4/C5 channels inhibits tumor cell line proliferation and confirms the TRPC4 target hypothesis generated by the cell line profiling. In selectivity assays englerin A weakly inhibits TRPA1, TRPV3/V4, and TRPM8 which suggests that englerin A may bind a common feature of TRP ion channels. In vivo experiments show that englerin A is lethal in rodents near doses needed to activate the TRPC4 channel. This toxicity suggests that englerin A itself is probably unsuitable for further drug development. However, since englerin A can be synthesized in the laboratory, it may be a useful chemical starting point to identify novel modulators of other TRP family channels. 相似文献
82.
Cristiano?L.P. Oliveira Priscila?R. Santos Andrea?M. Monteiro Antonio?M. Figueiredo?Neto 《Biophysical journal》2014,106(12):2595-2605
This work presents a controlled study of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) structural changes due to in vitro oxidation with copper ions. The changes were studied by small-angle x-ray scattering (SAXS) and dynamic light scattering (DLS) techniques in the case of LDL and by SAXS, DLS, and Z-scan (ZS) techniques in the case of HDL. SAXS data were analyzed with a to our knowledge new deconvolution method. This method provides the electron density profile of the samples directly from the intensity scattering of the monomers. Results show that LDL particles oxidized for 18 h show significant structural changes when compared to nonoxidized particles. Changes were observed in the electrical density profile, in size polydispersity, and in the degree of flexibility of the APO-B protein on the particle. HDL optical results obtained with the ZS technique showed a decrease of the amplitude of the nonlinear optical signal as a function of oxidation time. In contrast to LDL results reported in the literature, the HDL ZS signal does not lead to a complete loss of nonlinear optical signal after 18 h of copper oxidation. Also, the SAXS results did not indicate significant structural changes due to oxidation of HDL particles, and DLS results showed that a small number of oligomers formed in the sample oxidized for 18 h. All experimental results for the HDL samples indicate that this lipoprotein is more resistant to the oxidation process than are LDL particles. 相似文献
83.
Airoldi C Zona C Sironi E Colombo L Messa M Aurilia D Gregori M Masserini M Salmona M Nicotra F La Ferla B 《Journal of biotechnology》2010,156(4):317-324
Curcumin derivatives with high chemical stability, improved solubility and carrying a functionalized appendage for the linkage to other entities, have been synthesized in a straightforward manner. All compounds retained Curcumin ability to bind Aβ peptide oligomers without inducing their aggregation. Moreover all Curcumin derivatives were able to stain very efficiently Aβ deposits. 相似文献
84.
Eduardo Vilanova Cristiano Coutinho Guilherme Maia Paulo A. S. Mourão 《Cell and tissue research》2010,340(3):523-531
Marine sponges (Porifera) display an ancestral type of cell-cell adhesion, based on carbohydrate-carbohydrate interaction.
The aim of the present work was to investigate further details of this adhesion by using, as a model, the in vitro aggregation
of dissociated sponge cells. Our results showed the participation of sulfated polysaccharides in this cell-cell interaction,
as based on the following observations: (1) a variety of sponge cells contained similar sulfated polysaccharides as surface-associated
molecules and as intracellular inclusions; (2) 35S-sulfate metabolic labeling of dissociated sponge cells revealed that the majority (two thirds) of the total sulfated polysaccharide
occurred as a cell-surface-associated molecule; (3) the aggregation process of dissociated sponge cells demanded the active
de novo synthesis of sulfated polysaccharides, which ceased as cell aggregation reached a plateau; (4) the typical well-organized
aggregates of sponge cells, known as primmorphs, contained three cell types showing sulfated polysaccharides on their cell
surface; (5) collagen fibrils were also produced by the primmorphs in order to fill the extracellular spaces of their inner
portion and the external layer surrounding their entire surface. Our data have thus clarified the relevance of sulfated polysaccharides
in this system of in vitro sponge cell aggregation. The molecular basis of this system has practical relevance, since the
culture of sponge cells is necessary for the production of molecules with biotechnological applications. 相似文献
85.
Fabricio Fernandes Fontana Celso Tadeu Barbosa dos Santos Flavia Maria Esteves Ademir Rocha Geisa Ferreira Fernandes Cristiane Candida do Amaral Marcos Abel Domingues Zoilo Pires De Camargo Mario León Silva-Vergara 《Mycopathologia》2010,169(3):159-165
There is some evidence that dogs can be naturally infected by Paracoccidioides brasiliensis in endemic areas of paracoccidioidomycosis. In order to evaluate canine infection with this fungus, a survey with 149 urban
and 126 rural dogs was carried out using ELISA and intradermal tests with the gp43 antigen of P. brasiliensis in Uberaba, Minas Gerais state of Brazil. Forty-one out of 149 urban dogs were euthanatized and had their lungs, liver and
spleen removed. One slice from each viscera was processed for histopathological examination and the remaining was homogenized and then cultivated on mycobiotic agar
at room temperature and Fava-Netto medium at 35°C and observed for 12 weeks. Of urban dogs, 75 (50.3%) were small adult females,
56 (36%) were strays, while 93 (64%) had been donated to the municipal zoonosis control center. Nine (6.2%) had a positive
intradermal test without statistical differences regarding gender, race, nutritional status or origin. No colonies with microscopic
or morphology appearances resembling P. brasiliensis were isolated, nor granulomatous process or fungal structures were observed from histopathological examination. Eighty (53.6%)
of the urban dogs presented seroreactivity, without statistical differences regarding gender, race, nutritional state, origin,
or positive intradermal test. Of 126 rural dogs, 102 (80.5%) presented antibodies against gp43 antigen, and this was statistically
significant in relation to the reactivity detected in urban dogs (P = 0.0001). Thus, dogs are commonly infected with P. brasiliensis, but they probably present natural resistance to develop paracoccidioidomycosis. 相似文献
86.
Cinzia Ciccacci Carlo Perricone Fulvia Ceccarelli Sara Rufini Davide Di Fusco Cristiano Alessandri Francesca Romana Spinelli Enrica Cipriano Giuseppe Novelli Guido Valesini Paola Borgiani Fabrizio Conti 《PloS one》2014,9(11)
Background
Systemic lupus erythematosus (SLE) is an autoimmune disease with complex pathogenesis in which genes and environmental factors are involved. We aimed at analyzing previously identified loci associated with SLE or with other autoimmune and/or inflammatory disorders (STAT4, IL10, IL23R, IRAK1, PSORS1C1, HCP5, MIR146a, PTPN2, ERAP1, ATG16L1, IRGM) in a sample of Italian SLE patients in order to verify or confirm their possible involvement and relative contribution in the disease.Materials and methods
Two hundred thirty-nine consecutive SLE patients and 278 matched healthy controls were enrolled. Study protocol included complete physical examination, and clinical and laboratory data collection. Nineteen polymorphisms were genotyped by allelic discrimination assays. A case-control association study and a genotype-phenotype correlation were performed.Results
STAT4 was the most associated gene [P = 3×10−7, OR = 2.13 (95% CI: 1.59–2.85)]. IL10 confirmed its association with SLE [rs3024505: P = 0.02, OR = 1.52 (95% CI: 1.07–2.16)]. We describe a novel significant association between HCP5 locus and SLE susceptibility [rs3099844: P = 0.01, OR = 2.06 (95% CI: 1.18–3.6)]. The genotype/phenotype correlation analysis showed several associations including a higher risk to develop pericarditis with STAT4, and an association between HCP5 rs3099844 and anti-Ro/SSA antibodies.Conclusions
STAT4 and IL10 confirm their association with SLE. We found that some SNPs in PSORS1C1, ATG16L1, IL23R, PTPN2 and MIR146a genes can determine particular disease phenotypes. HCP5 rs3099844 is associated with SLE and with anti-Ro/SSA. This polymorphism has been previously found associated with cardiac manifestations of SLE, a condition related with anti-Ro/SSA antibodies. Thus, our results may provide new insights into SLE pathogenesis. 相似文献87.
Collagen peptides modulate the metabolism of extracellular matrix by human dermal fibroblasts derived from sun‐protected and sun‐exposed body sites 下载免费PDF全文
Vivian Zague Jonatas Bussador do Amaral Paula Rezende Teixeira Evandro Luis de Oliveira Niero Camila Lauand Glaucia Maria Machado‐Santelli 《Cell biology international》2018,42(1):95-104
Clinical data published in recent years have demonstrated positive effects of collagen hydrolysate (CH) on skin aging clinical signs. CH use as food supplement has a long history; however, few studies have addressed the underlying purpose of CH on the cellular and molecular biology of skin cells that could elucidate clinical improvement findings. Wide diversity of characteristics has been reported for dermal fibroblasts derived from different body sites and it is unknown whether collagen peptides could modulate differently cells from chronological aged and photoaged skin areas. This study investigated the influence of CH on the extracellular matrix metabolism and proliferation of human dermal fibroblasts (HDFs) derived from chronological aged (sun‐protected) and photoaged (sun‐exposed) body sites. CH treatment did not affect cellular proliferation of either cell cultures, but notably modulated cell metabolism in monolayer model, increasing the content of dermal matrix precursor and main protein, procollagen I and collagen I, respectively. These effects were confirmed in the human dermal equivalent model. The increase in collagen content in the cultures was attributed to stimulation of biosynthesis and decreased collagen I metabolism through inhibition of metalloproteinase activity (MMP) 1 and 2. Modulation of CH in dermal metabolism did not differ between cells derived from sun‐protected and sun‐exposed areas, although lower concentrations of CH seemed to be enough to stimulate sun‐exposed‐derived HDFs, suggesting more pronounced effect in these cells. This study contributes to understanding the biological effects of CH on skin cells and viability of its use as a functional ingredient in food supplements. 相似文献
88.
Carolina G. Fernandes Guilhian Leipnitz Bianca Seminotti Alexandre U. Amaral Ângela Zanatta Carmen R. Vargas Carlos S. Dutra Filho Moacir Wajner 《Cellular and molecular neurobiology》2010,30(2):317-326
High levels of phenylalanine (Phe) are the biochemical hallmark of phenylketonuria (PKU), a neurometabolic disorder clinically
characterized by severe mental retardation and other brain abnormalities, including cortical atrophy and microcephaly. Considering
that the pathomechanisms leading to brain damage and particularly the marked cognitive impairment in this disease are poorly
understood, in the present study we investigated the in vitro effect of Phe, at similar concentrations as to those found in
brain of PKU patients, on important parameters of oxidative stress in the hippocampus and cerebral cortex of developing rats.
We found that Phe induced in vitro lipid peroxidation (increase of TBA-RS values) and protein oxidative damage (sulfhydryl
oxidation) in both cerebral structures. Furthermore, these effects were probably mediated by reactive oxygen species, since
the lipid oxidative damage was totally prevented by the free radical scavengers α-tocopherol and melatonin, but not by L-NAME,
a potent inhibitor of nitric oxide synthase. Accordingly, Phe did not induce nitric oxide synthesis, but significantly decreased
the levels of reduced glutathione (GSH), the major brain antioxidant defense, in hippocampus and cerebral cortex supernatants.
Phe also reduced the thiol groups of a commercial GSH solution in a cell-free medium. We also found that the major metabolites
of Phe catabolism, phenylpyruvate, phenyllactate and phenylacetate also increased TBA-RS levels in cerebral cortex, but to
a lesser degree. The data indicate that Phe elicits oxidative stress in the hippocampus, a structure mainly involved with
learning/memory, and also in the cerebral cortex, which is severely damaged in PKU patients. It is therefore presumed that
this pathomechanism may be involved at least in part in the severe cognitive deficit and in the characteristic cortical atrophy
associated with dysmyelination and leukodystrophy observed in this disorder. 相似文献
89.
Souza DG Fagundes CT Amaral FA Cisalpino D Sousa LP Vieira AT Pinho V Nicoli JR Vieira LQ Fierro IM Teixeira MM 《Journal of immunology (Baltimore, Md. : 1950)》2007,179(12):8533-8543
The appropriate development of an inflammatory response is central for the ability of a host to deal with any infectious insult. However, excessive, misplaced, or uncontrolled inflammation may lead to acute or chronic diseases. The microbiota plays an important role in the control of inflammatory responsiveness. In this study, we investigated the role of lipoxin A4 and annexin-1 for the IL-10-dependent inflammatory hyporesponsiveness observed in germfree mice. Administration of a 15-epi-lipoxin A4 analog or an annexin-1-derived peptide to conventional mice prevented tissue injury, TNF-alpha production, and lethality after intestinal ischemia/reperfusion. This was associated with enhanced IL-10 production. Lipoxin A4 and annexin-1 failed to prevent reperfusion injury in IL-10-deficient mice. In germfree mice, there was enhanced expression of both lipoxin A4 and annexin-1. Blockade of lipoxin A4 synthesis with a 5-lipoxygenase inhibitor or Abs against annexin-1 partially prevented IL-10 production and this was accompanied by partial reversion of inflammatory hyporesponsiveness in germfree mice. Administration of BOC-1, an antagonist of ALX receptors (at which both lipoxin A4 and annexin-1 act), or simultaneous administration of 5-lipoxygenase inhibitor and anti-annexin-1 Abs, was associated with tissue injury, TNF-alpha production, and lethality similar to that found in conventional mice. Thus, our data demonstrate that inflammatory responsiveness is tightly controlled by the presence of the microbiota and that the innate capacity of germfree mice to produce IL-10 is secondary to their endogenous greater ability to produce lipoxin A4 and annexin-1. 相似文献
90.