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Tsuyoshi Sakai Hyun Suk Jung Osamu Sato Masafumi D. Yamada Dong-Ju You Reiko Ikebe Mitsuo Ikebe 《The Journal of biological chemistry》2015,290(28):17587-17598
Human myosin VIIA (HM7A) is responsible for human Usher syndrome type 1B, which causes hearing and visual loss in humans. Here we studied the regulation of HM7A. The actin-activated ATPase activity of full-length HM7A (HM7AFull) was lower than that of tail-truncated HM7A (HM7AΔTail). Deletion of the C-terminal 40 amino acids and mutation of the basic residues in this region (R2176A or K2179A) abolished the inhibition. Electron microscopy revealed that HM7AFull is a monomer in which the tail domain bends back toward the head-neck domain to form a compact structure. This compact structure is extended at high ionic strength or in the presence of Ca2+. Although myosin VIIA has five isoleucine-glutamine (IQ) motifs, the neck length seems to be shorter than the expected length of five bound calmodulins. Supporting this observation, the IQ domain bound only three calmodulins in Ca2+, and the first IQ motif failed to bind calmodulin in EGTA. These results suggest that the unique IQ domain of HM7A is important for the tail-neck interaction and, therefore, regulation. Cellular studies revealed that dimer formation of HM7A is critical for its translocation to filopodial tips and that the tail domain (HM7ATail) markedly reduced the filopodial tip localization of the HM7AΔTail dimer, suggesting that the tail-inhibition mechanism is operating in vivo. The translocation of the HM7AFull dimer was significantly less than that of the HM7AΔTail dimer, and R2176A/R2179A mutation rescued the filopodial tip translocation. These results suggest that HM7A can transport its cargo molecules, such as USH1 proteins, upon release of the tail-dependent inhibition. 相似文献
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Interleukin 10 (IL-10) is a multifunctional cytokine that regulates diverse functions of immune cells. Natural killer (NK)
cells express the IL-10 and IL-10 receptor, but little is known about the function of IL-10 on NK cell activation. In this
study, we show the expression and role of IL-10 in human NK cells. Among the cytokines tested, IL-15 was the most potent inducer
of IL-10, with a maximal peak expression at 5 h after treatment. Furthermore, IL-10 receptor was shown to be expressed in
NK cells. IL-10 alone had a significant effect on NK cytotoxicity which additively increased NK cell cytotoxicity in the presence
of IL-15. Neutralizing IL-10 with anti-IL-10 antibody suppressed the inductive effect of IL-10 on NK cell cytotoxicity; however,
IL-10 had no effect on IFN-γ or TNF-α production or NK cell activatory receptor expression. STAT signals are implicated as
a key mediator of IL-10/IL-15 cytotoxicity response. Thus, the effect of IL-10 on NK cells is particularly interesting with
regard to the STAT3 signal that was enhanced by IL-10 or IL-15. 相似文献
126.
Epstein-Barr virus (EBV) is associated with human cancers such as nasopharyngeal carcinoma, Burkitt’s lymphoma, Hodgkin’s
disease, and gastric carcinoma (GC). EBV is associated with about 10% of all GC cases globally. EBV-associated GC has distinct
features from EBV-negative GC. However, it is still unclear if EBV infection has any effect on GC chemoresistance. Cell proliferation
assay, cell cycle analysis, and active caspase Western blot revealed that the EBV-positive GC cell line (AGS-EBV) showed chemoresistance
to docetaxel compared to the EBV-negative GC cell line (AGS). Docetaxel treatment increased expression of Bax similarly in
AGS and AGS-EBV cell lines. However, Bcl-2 induction was markedly higher in AGS-EBV cells, after docetaxel treatment. Although
docetaxel increased the expression of p53 to a similar extent in both cell lines, induction of p21 in AGS-EBV cells was lower
than in AGS cells. Furthermore, expression of survivin was higher in AGS-EBV cells than in AGS cells following docetaxel treatment
as well as at basal state. EBVlytic gene expression was induced by docetaxel treatment in AGS-EBV cells. The results suggest
that EBV infection and lytic induction confers chemoresistance to GC, possibly by regulating cellular and EBV latent and lytic
gene expression. 相似文献
127.
Zmorzynska A Suk JE Biederbick W Maidhof H Sasse J Semenza JC Hunger I 《Biosecurity and bioterrorism : biodefense strategy, practice, and science》2011,9(4):372-378
Biotechnological research poses a special security problem because of the duality between beneficial use and misuse. In order to find a balance between regulating potentially dangerous research and assuring scientific advancement, a number of assessments have tried to define which types of research are especially open to misuse and should therefore be considered dual-use research of special concern requiring rigorous oversight. So far, there has been no common understanding of what such activities are. Here we present a review of 27 assessments focusing on biological dual-use issues published between 1997 and 2008. Dual-use research activities identified by these assessments as being of special concern were compiled and compared. Moreover, from these 27 assessments, the primary research publications explicitly identified as examples of concerning research activities were extracted and analyzed. We extracted a core list of 11 activities of special concern and show that this list does not match with the reasons why primary research publications were identified as being of special concern. Additionally, we note that the 11 activities identified are not easily conducted or replicated, and therefore the likelihood of their being used in a high-tech mass casualty bioterrorism event should be reevaluated. 相似文献
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Introduction
The vast difference in the abundance of different proteins in biological samples limits the determination of the complete proteome of a cell type, requiring fractionation of proteins and peptides before MS analysis. 相似文献130.
Background: We hypothesize that pH difference between acid‐secreting corpus and non‐secreting antrum might influence the activity of H. pylori’s urease and/or related genes. We therefore measured urease activity and the expression of amiE whose encoded protein that hydrolyzes short‐chain amides to produce ammonia. Materials and Methods: Fifty‐four patients were recruited into this study. Each gastroscopic biopsy specimen collected from the antrum and body of each patient was immediately used to measure urease activity using serial changes of urease activity (ammonia levels) during 60 minutes. Probe specific for amiE was labeled with a biotin nick‐translation kit and was used to detect expression of these genes (mRNA) in fresh‐frozen gastroscopic biopsy specimens using fluorescent in situ hybridization (FISH). Results: Urease activity at 60 minutes from the gastric antrum and body of all patients infected with H. pylori was 399.5 ± 490.5 and 837.9 ± 1038.9 μg/dL, respectively (p = .004). Urease activity in the antrum was correlated with H. pylori density. Urease activity or H. pylori density in the antrum was significantly correlated with chronic active inflammation; in contrast, this correlation was not found in the gastric body. The expression level of amiE was 1.5 times higher (p < .05) in the gastric body compared with the antrum. Conclusion: Topographically, the urease activity in body was much higher than in antrum. The expression level of amiE was higher in the gastric body compared with the antrum. 相似文献