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排序方式: 共有172条查询结果,搜索用时 31 毫秒
131.
132.
M402, a novel heparan sulfate mimetic, targets multiple pathways implicated in tumor progression and metastasis 总被引:1,自引:0,他引:1
Zhou H Roy S Cochran E Zouaoui R Chu CL Duffner J Zhao G Smith S Galcheva-Gargova Z Karlgren J Dussault N Kwan RY Moy E Barnes M Long A Honan C Qi YW Shriver Z Ganguly T Schultes B Venkataraman G Kishimoto TK 《PloS one》2011,6(6):e21106
Heparan sulfate proteoglycans (HSPGs) play a key role in shaping the tumor microenvironment by presenting growth factors, cytokines, and other soluble factors that are critical for host cell recruitment and activation, as well as promoting tumor progression, metastasis, and survival. M402 is a rationally engineered, non-cytotoxic heparan sulfate (HS) mimetic, designed to inhibit multiple factors implicated in tumor-host cell interactions, including VEGF, FGF2, SDF-1α, P-selectin, and heparanase. A single s.c. dose of M402 effectively inhibited seeding of B16F10 murine melanoma cells to the lung in an experimental metastasis model. Fluorescent-labeled M402 demonstrated selective accumulation in the primary tumor. Immunohistological analyses of the primary tumor revealed a decrease in microvessel density in M402 treated animals, suggesting anti-angiogenesis to be one of the mechanisms involved in-vivo. M402 treatment also normalized circulating levels of myeloid derived suppressor cells in tumor bearing mice. Chronic administration of M402, alone or in combination with cisplatin or docetaxel, inhibited spontaneous metastasis and prolonged survival in an orthotopic 4T1 murine mammary carcinoma model. These data demonstrate that modulating HSPG biology represents a novel approach to target multiple factors involved in tumor progression and metastasis. 相似文献
133.
Dominic Dussault Khanh Dang Vu Monique Lacroix 《Probiotics and antimicrobial proteins》2016,8(3):170-175
Lactococcus lactis subsp lactis BSA (L. lactis BSA) was isolated from a commercial fermented product (BSA Food Ingredients, Montreal, Canada) containing mixed bacteria that are used as starter for food fermentation. In order to increase the bacteriocin production by L. lactis BSA, different fermentation conditions were conducted. They included different volumetric combinations of two culture media (the Man, Rogosa and Sharpe (MRS) broth and skim milk), agitation level (0 and 100 rpm) and concentration of commercial nisin (0, 0.15, and 0.30 µg/ml) added into culture media as stimulant agent for nisin production. During fermentation, samples were collected and used for antibacterial evaluation against Lactobacillus sakei using agar diffusion assay. Results showed that medium containing 50 % MRS broth and 50 % skim milk gave better antibacterial activity as compared to other medium formulations. Agitation (100 rpm) did not improve nisin production by L. lactis BSA. Adding 0.15 µg/ml of nisin into the medium-containing 50 % MRS broth and 50 % skim milk caused the highest nisin activity of 18,820 AU/ml as compared to other medium formulations. This activity was 4 and ~3 times higher than medium containing 100 % MRS broth without added nisin (~4700 AU/ml) and 100 % MRS broth with 0.15 µg/ml of added nisin (~6650 AU/ml), respectively. 相似文献
134.
Alessandro A. Boezio Loren Berry Brian K. Albrecht David Bauer Steven F. Bellon Christiane Bode April Chen Deborah Choquette Isabelle Dussault Satoko Hirai Paula Kaplan-Lefko Jay F. Larrow Min-Hwa Jasmine Lin Julia Lohman Michele H. Potashman Karen Rex Michael Santostefano Kavita Shah Roman Shimanovich Stephanie K. Springer Yohannes Teffera Yajing Yang Yihong Zhang Jean-Christophe Harmange 《Bioorganic & medicinal chemistry letters》2009,19(22):6307-6312
Deregulation of the receptor tyrosine kinase c-Met has been implicated in several human cancers and is an attractive target for small molecule drug discovery. We previously showed that O-linked triazolopyridazines can be potent inhibitors of c-Met. Herein, we report the discovery of a related series of N-linked triazolopyridazines which demonstrate nanomolar inhibition of c-Met kinase activity and display improved pharmacodynamic profiles. Specifically, the potent time-dependent inhibition of cytochrome P450 associated with the O-linked triazolopyridazines has been eliminated within this novel series of inhibitors. N-linked triazolopyridazine 24 exhibited favorable pharmacokinetics and displayed potent inhibition of HGF-mediated c-Met phosphorylation in a mouse liver PD model. Once-daily oral administration of 24 for 22 days showed significant tumor growth inhibition in an NIH-3T3/TPR-Met xenograft mouse efficacy model. 相似文献
135.
Estimation of the membrane potential of cultured macrophages from the fast potential transient upon microelectrode entry 总被引:3,自引:1,他引:2 下载免费PDF全文
Analysis of membrane potential recordings upon microelectrode impalement of four types of macrophages (cell lines P388D1 and PU5-1.8, cultured mouse peritoneal macrophages, and cultured human monocytes) reveals that these cells have membrane potentials at least two times more negative than sustained potential values (E(s)) frequently reported. Upon microelectrode entry into the cell (P388D1), the recorded potential drops to a peak value (E(p)) (mean -37 mV for 50 cells, range -15 to -70 mV) within 2 ms, after which it decays to a depolarized potential (E(n)) (mean -12 mV) in about 20 ms. Thereafter, the membrane develops one or a series of slow hyperpolarizations before a final sustained membrane potential (E(s)) (mean -14 mV, range -5 to -40) is established. The mean value of the peak of the first hyperpolarization (E(h)) is -30 mV (range -10 to -55 mV). The initial fast peak transient, measured upon microelectrode entry, was first described and analyzed by Lassen et al. (Lassen, U.V., A.M. T. Nielson, L. Pape, and L. O. Simonsen, 1971, J. Membr. Biol. 6:269-288 for other change in the membrane potential from its real value before impalement to a sustained depolarized value. This was shown to be true for macrophages by two-electrode impalements of single cells. Values of E(p), E(n), E(h), E(s), and membrane resistance (R(m)) measured for the other macrophages were similar to those of P388D1. From these results we conclude that E(p) is a better estimate of the true membrane potential of macrophages than E(s), and that the slow hyperpolarizations upon impalement should be regarded as transient repolarizations back to the original membrane potentials. Thus, analysis of the initial fast impalement transient can be a valuable aid in the estimation of the membrane potential of various sorts of small isolated cells by microelectrodes. 相似文献
136.
Measurement of blood fluorocarbon levels was carried out in subjects exposed to a number of household aerosol products containing fluorocarbon gases as propellants. All aerosols were used according to manufacturers'' recommendations. The general purpose of the study was to determine whether with normal routine exposure to a wide variety of household aerosol products fluorocarbon could be found in the blood and if so, to check the potential toxicity of the levels reached. Daily exposure to aerosols according to the study regimen lasted four consecutive weeks; this period was preceded and followed by two weeks of abstention from exposure. At the end of each of the three periods a medical examination, including evaluation of cardiac function, respiratory function studies, and hematological and functional clinical biochemical tests was performed. All tests and assessments failed to show any indication of toxicity. No trace of fluorocarbon was found in any of the blood sampled at intervals during the study. 相似文献
137.
138.
The 3,5,3'-triiodothyronine (T3) binding activity of solubilized nuclear proteins from rat liver was decreased when molybdate (10 mM) was present in the incubation medium in the absence of thiol reagents. The equilibrium affinity constant was reduced by 40%. The rate of degradation of T3-receptor complexes at 37 degrees C remained unchanged, but when the extracts were further reincubated in the presence of beta-mercaptoethanol, molybdate had a protective effect after 5 h incubation at 37 degrees C. In contrast, the thyroxine (T4) binding activity was not affected by heating at 37 degrees C or by molybdate. Ion-exchange chromatography confirmed the existence of a molybdate-receptor interaction: the T3-receptor complexes shifted from elution at 0.22 to 0.20 M NaCl with the progressive appearance of a small leader peak, whereas the T4-receptor complexes eluted in a large and split peak (0.22-0.4 M NaCl). The destabilizing effect on T3 binding induced by exogenous dephosphorylation is more efficiently reversed by beta-mercaptoethanol when the extracts were pretreated by molybdate. In controls, the loss of saturable T3 binding activity was recovered by 50% at a 10 mM concentration of beta-mercaptoethanol, but in the presence of molybdate, the loss of T3 binding activity was recovered by 50% at a 5 mM concentration of beta-mercaptoethanol. This molybdate-receptor interaction is similar to that with nuclear receptor models in term of (i) stabilization of hormone binding, (ii) dependency on a thiol, and (iii) reversibility of the destabilizing effect by exogenous dephosphorylation. 相似文献
139.
Sze SH; Roytberg MA; Gelfand MS; Mironov AA; Astakhova TV; Pevzner PA 《Bioinformatics (Oxford, England)》1998,14(1):14-19
MOTIVATION: Gene annotation is the final goal of gene prediction
algorithms. However, these algorithms frequently make mistakes and
therefore the use of gene predictions for sequence annotation is hardly
possible. As a result, biologists are forced to conduct time-consuming gene
identification experiments by designing appropriate PCR primers to test
cDNA libraries or applying RT-PCR, exon trapping/amplification, or other
techniques. This process frequently amounts to 'guessing' PCR primers on
top of unreliable gene predictions and frequently leads to wasting of
experimental efforts. RESULTS: The present paper proposes a simple and
reliable algorithm for experimental gene identification which bypasses the
unreliable gene prediction step. Studies of the performance of the
algorithm on a sample of human genes indicate that an experimental protocol
based on the algorithm's predictions achieves an accurate gene
identification with relatively few PCR primers. Predictions of PCR primers
may be used for exon amplification in preliminary mutation analysis during
an attempt to identify a gene responsible for a disease. We propose a
simple approach to find a short region from a genomic sequence that with
high probability overlaps with some exon of the gene. The algorithm is
enhanced to find one or more segments that are probably contained in the
translated region of the gene and can be used as PCR primers to select
appropriate clones in cDNA libraries by selective amplification. The
algorithm is further extended to locate a set of PCR primers that uniformly
cover all translated regions and can be used for RT-PCR and further
sequencing of (unknown) mRNA.
相似文献
140.
The clock gene period (per) controls a number of biological rhythms in
Drosophila. In D. melanogaster, per has a repetitive region that encodes a
number of alternating threonine-glycine residues. We sequenced and compared
this region from several different Drosophila species belonging to various
groups within the Drosophila and Sophophora subgenera. This part of per
shows a great variability in both DNA sequence and length. Furthermore,
analysis of the data suggests that changes in the length of this variable
region might be associated with amino acid replacements in the more
conserved flanking sequences.
相似文献