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排序方式: 共有298条查询结果,搜索用时 15 毫秒
31.
Dustin Nash Cammon B. Arrington Brett J. Kennedy Mark Yandell Wilfred Wu Wenying Zhang Stephanie Ware Lynn B. Jorde Peter J. Gruber H. Joseph Yost Neil E. Bowles Steven B. Bleyl 《PloS one》2015,10(6)
Most isolated congenital heart defects are thought to be sporadic and are often ascribed to multifactorial mechanisms with poorly understood genetics. Total Anomalous Pulmonary Venous Return (TAPVR) occurs in 1 in 15,000 live-born infants and occurs either in isolation or as part of a syndrome involving aberrant left-right development. Previously, we reported causative links between TAVPR and the PDGFRA gene. TAPVR has also been linked to the ANKRD1/CARP genes. However, these genes only explain a small fraction of the heritability of the condition. By examination of phased single nucleotide polymorphism genotype data from 5 distantly related TAPVR patients we identified a single 25 cM shared, Identical by Descent genomic segment on the short arm of chromosome 12 shared by 3 of the patients and their obligate-carrier parents. Whole genome sequence (WGS) analysis identified a non-synonymous variant within the shared segment in the retinol binding protein 5 (RBP5) gene. The RBP5 variant is predicted to be deleterious and is overrepresented in the TAPVR population. Gene expression and functional analysis of the zebrafish orthologue, rbp7, supports the notion that RBP5 is a TAPVR susceptibility gene. Additional sequence analysis also uncovered deleterious variants in genes associated with retinoic acid signaling, including NODAL and retinol dehydrogenase 10. These data indicate that genetic variation in the retinoic acid signaling pathway confers, in part, susceptibility to TAPVR. 相似文献
32.
Nesbitt TL Patel PA Yost MJ Goodwin RL Potts JD 《In vitro cellular & developmental biology. Animal》2007,43(1):10-16
Coronary vascular disease is one of the leading causes of mortality and morbidity in the United States. Therefore, a mechanistic
understanding of coronary vessel morphogenesis would aid in the innovation of new therapies targeting vascular disorders.
Moreover, a functionally equivalent in vitro model system allows for the delineation of the molecular mechanisms that regulate
coronary vessel development. In this study, we present a novel in vitro model system. This three-dimensional (3-D) model system
consists of a tubular scaffold, which is engineered from type-I collagen and has been optimized to support the growth of embryonic
cardiac tissues. In this report, proepicardial (PE) cells, the developmental precursors of coronary vessels, have been isolated
from several model species and cultured on this scaffold. In this model system, the PE cells were able to recapitulate several
aspects of coronary vessel morphogenesis including epicardial formation, the epicardial to mesenchymal transformation, and
de novo coronary vessel development or vasculogenesis. The differentiation of PE cells was characterized using a variety of
specific protein markers. The potential uses of this novel coronary developmental model are discussed. 相似文献
33.
Noncanonical Wnt signals control morphogenetic movements during vertebrate gastrulation. Casein kinase I epsilon (CKIvarepsilon) is a Wnt-regulated kinase that regulates Wnt/beta-catenin signaling and has a beta-catenin-independent role(s) in morphogenesis that is poorly understood. Here we report the identification of a CKIvarepsilon binding partner, SIPA1L1/E6TP1, a GAP (GTPase activating protein) of the Rap small GTPase family. We show that CKIvarepsilon phosphorylates SIPA1L1 to reduce its stability and thereby increase Rap1 activation. Wnt-8, which activates CKIvarepsilon, enhances the CKIvarepsilon-dependent phosphorylation and degradation of SIPA1L1. In early Xenopus or zebrafish development, inactivation of the Rap1 pathway results in abnormal gastrulation and a shortened anterior-posterior axis. Although CKIvarepsilon also transduces Wnt/beta-catenin signaling, inhibition of Rap1 does not alter beta-catenin-regulated gene expression. Our data demonstrate a role for CKIvarepsilon in noncanonical Wnt signaling and indicate that Wnt regulates morphogenesis in part through CKIvarepsilon-mediated control of Rap1 signaling. 相似文献
34.
Kraemer BF Campbell RA Schwertz H Cody MJ Franks Z Tolley ND Kahr WH Lindemann S Seizer P Yost CC Zimmerman GA Weyrich AS 《PLoS pathogens》2011,7(11):e1002355
Human β-defensins (hBD) are antimicrobial peptides that curb microbial activity. Although hBD's are primarily expressed by epithelial cells, we show that human platelets express hBD-1 that has both predicted and novel antibacterial activities. We observed that activated platelets surround Staphylococcus aureus (S. aureus), forcing the pathogens into clusters that have a reduced growth rate compared to S. aureus alone. Given the microbicidal activity of β-defensins, we determined whether hBD family members were present in platelets and found mRNA and protein for hBD-1. We also established that hBD-1 protein resided in extragranular cytoplasmic compartments of platelets. Consistent with this localization pattern, agonists that elicit granular secretion by platelets did not readily induce hBD-1 release. Nevertheless, platelets released hBD-1 when they were stimulated by α-toxin, a S. aureus product that permeabilizes target cells. Platelet-derived hBD-1 significantly impaired the growth of clinical strains of S. aureus. hBD-1 also induced robust neutrophil extracellular trap (NET) formation by target polymorphonuclear leukocytes (PMNs), which is a novel antimicrobial function of β-defensins that was not previously identified. Taken together, these data demonstrate that hBD-1 is a previously-unrecognized component of platelets that displays classic antimicrobial activity and, in addition, signals PMNs to extrude DNA lattices that capture and kill bacteria. 相似文献
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Cilia are highly conserved organelles that have diverse motility and sensory functions. Recent discoveries have revealed that cilia also have crucial roles in cell signaling pathways and in maintaining cellular homeostasis. As such, defects in cilia formation or function have profound effects on the development of body pattern and the physiology of multiple organ systems. By categorizing syndromes that are due to cilia dysfunction in humans and from studies in vertebrate model organisms, molecular pathways that intersect with cilia formation and function have come to light. Here, we summarize an emerging view that in order to understand some complex developmental pathways and disease etiologies, one must consider the molecular functions performed by cilia. 相似文献
39.
CYP4B1 is highly expressed in rat nasal respiratory mucosa, and to a lesser extent in olfactory mucosa. Examination of high-power photomicrographs suggests that CYP4B1 may be a secreted protein, based on the fact that immunoreactivity appears to be present in the lumens of ducts of Bowman's glands (rather than intracellular localization, as we observed with an antibody recognizing CYP2F4) and in secretory granules in respiratory mucosa. Furthermore, anti-CYP4B1 immunoreactivity is present on the surface of both respiratory and olfactory mucosa. We used SignalP 3.0 analysis to ascertain the likelihood that rat CYP4B1 is a secreted protein. While this analysis does not suggest that rat CYP4B1 is a secreted protein, several other cytochrome P450 enzymes were predicted to be secreted proteins. The observation that multiple human cytochrome P450s appear to be secreted proteins helps to explain the appearance of anti-cytochrome P450 antigens in cases of human autoimmune liver diseases. 相似文献
40.
Eui-Ju Hong Se-Hyung Park Kyung-Chul Choi Peter CK Leung Eui-Bae Jeung 《Reproductive biology and endocrinology : RB&E》2006,4(1):49-12
Environmental estrogenic compounds which bind to the estrogen receptor (ER) can block or alter endogenous functions of estrogen
in reproductive and developmental stages. A microarray technology is a very valuable method for the prediction of hormone-responsive
activities in various gene expressions. Thus, we investigated the altered gene expression by estrogen and endocrine disruptors
(EDs) using microarray technology in the uterus of immature rats. In this study, the expression levels of only 555 genes (7.42%)
among the 7636 genes spotted on microarray chips were enhanced by more than two-fold following treatment with estradiol (E2),
suggesting that direct or rapid response to E2 is widespread at the mRNA levels in these genes. In addition, elevated expression
levels of the genes (over 2-fold) were observed by diethylstilbestrol (DES; 9.01%), octyl-phenol (OP; 8.81%), nonyl-phenol
(NP; 9.51%), bisphenol-A (BPA; 8.26%) or genistein (9.97%) in the uterus of immature rats. The expression levels of representative
genes, i.e., calbindin-D9k (CaBP-9k; vitamin D-dependent calcium-binding protein), oxytocin, adipocyte complement related
protein (MW 30 kDa), lactate dehydrogenase A and calcium binding protein A6 (S100a6; calcyclin), were confirmed in these tissues
by real-time PCR. In addition, the mRNA levels of these genes by real-time PCR were increased at follicular phase when E2
level was elevated during estrous cycle of adult female rats. In conclusion, these results indicate distinct altered expression
of responsive genes following exposure to E2 and estrogenic compounds, and implicate distinct effects of endogenous E2 and
environmental endocrine disrupting chemicals in the uterus of immature rats. 相似文献