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71.
Yao Y Fan Y Wu J Wan H Wang J Lam S Lam WL Girard L Gazdar AF Wu Z Zhou Q 《Biochemical and biophysical research communications》2012,423(3):613-619
To identify a panel of tumor associated autoantibodies which can potentially be used as biomarkers for the early diagnosis of non-small cell lung cancer (NSCLC). Thirty-five unique and in-frame expressed phage proteins were isolated. Based on the gene expression profiling, four proteins were selected for further study. Both receiver operating characteristic curve analysis and leave-one-out method revealed that combined measurements of four antibodies produced have better predictive accuracies than any single marker alone. Leave-one-out validation also showed significant relevance with all stages of NSCLC patients. The panel of autoantibodies has a high potential for detecting early stage NSCLC. 相似文献
72.
Lopez-Herrera G Tampella G Pan-Hammarström Q Herholz P Trujillo-Vargas CM Phadwal K Simon AK Moutschen M Etzioni A Mory A Srugo I Melamed D Hultenby K Liu C Baronio M Vitali M Philippet P Dideberg V Aghamohammadi A Rezaei N Enright V Du L Salzer U Eibel H Pfeifer D Veelken H Stauss H Lougaris V Plebani A Gertz EM Schäffer AA Hammarström L Grimbacher B 《American journal of human genetics》2012,90(6):986-1001
Most autosomal genetic causes of childhood-onset hypogammaglobulinemia are currently not well understood. Most affected individuals are simplex cases, but both autosomal-dominant and autosomal-recessive inheritance have been described. We performed genetic linkage analysis in consanguineous families affected by hypogammaglobulinemia. Four consanguineous families with childhood-onset humoral immune deficiency and features of autoimmunity shared genotype evidence for a linkage interval on chromosome 4q. Sequencing of positional candidate genes revealed that in each family, affected individuals had a distinct homozygous mutation in LRBA (lipopolysaccharide responsive beige-like anchor protein). All LRBA mutations segregated with the disease because homozygous individuals showed hypogammaglobulinemia and autoimmunity, whereas heterozygous individuals were healthy. These mutations were absent in healthy controls. Individuals with homozygous LRBA mutations had no LRBA, had disturbed B cell development, defective in vitro B cell activation, plasmablast formation, and immunoglobulin secretion, and had low proliferative responses. We conclude that mutations in LRBA cause an immune deficiency characterized by defects in B cell activation and autophagy and by susceptibility to apoptosis, all of which are associated with a clinical phenotype of hypogammaglobulinemia and autoimmunity. 相似文献
73.
Carlin D Sepich D Grover VK Cooper MK Solnica-Krezel L Inbal A 《Development (Cambridge, England)》2012,139(14):2614-2624
Six3 exerts multiple functions in the development of anterior neural tissue of vertebrate embryos. Whereas complete loss of Six3 function in the mouse results in failure of forebrain formation, its hypomorphic mutations in human and mouse can promote holoprosencephaly (HPE), a forebrain malformation that results, at least in part, from abnormal telencephalon development. However, the roles of Six3 in telencephalon patterning and differentiation are not well understood. To address the role of Six3 in telencephalon development, we analyzed zebrafish embryos deficient in two out of three Six3-related genes, six3b and six7, representing a partial loss of Six3 function. We found that telencephalon forms in six3b;six7-deficient embryos; however, ventral telencephalic domains are smaller and dorsal domains are larger. Decreased cell proliferation or excess apoptosis cannot account for the ventral deficiency. Instead, six3b and six7 are required during early segmentation for specification of ventral progenitors, similar to the role of Hedgehog (Hh) signaling in telencephalon development. Unlike in mice, we observe that Hh signaling is not disrupted in embryos with reduced Six3 function. Furthermore, six3b overexpression is sufficient to compensate for loss of Hh signaling in isl1- but not nkx2.1b-positive cells, suggesting a novel Hh-independent role for Six3 in telencephalon patterning. We further find that Six3 promotes ventral telencephalic fates through transient regulation of foxg1a expression and repression of the Wnt/β-catenin pathway. 相似文献
74.
75.
Direct animal behavior can be inferred from the fossil record only in exceptional circumstances. The exceptional mode of preservation of ammonoid shells in the Posidonia Shale (Lower Jurassic, lower Toarcian) of Dotternhausen in southern Germany, with only the organic periostracum preserved, provides an excellent opportunity to observe the contents of the ammonoid body chamber because this periostracum is translucent. Here, we report upon three delicate lobsters preserved within a compressed ammonoid specimen of Harpoceras falciferum. We attempt to explain this gregarious behavior. The three lobsters were studied using standard microscopy under low angle light. The lobsters belong to the extinct family of the Eryonidae; further identification was not possible. The organic material of the three small lobsters is preserved more than halfway into the ammonoid body chamber. The lobsters are closely spaced and are positioned with their tails oriented toward each other. The specimens are interpreted to represent corpses rather than molts. The lobsters probably sought shelter in preparation for molting or against predators such as fish that were present in Dotternhausen. Alternatively, the soft tissue of the ammonoid may have been a source of food that attracted the lobsters, or it may have served as a long-term residency for the lobsters (inquilinism). The lobsters represent the oldest known example of gregariousness amongst lobsters and decapods in the fossil record. Gregarious behavior in lobsters, also known for extant lobsters, thus developed earlier in earth's history than previously known. Moreover, this is one of the oldest known examples of decapod crustaceans preserved within cephalopod shells. 相似文献
76.
Nadler C Koby S Peleg A Johnson AC Suddala KC Sathiyamoorthy K Smith BE Saper MA Rosenshine I 《PloS one》2012,7(6):e37984
Capsules frequently play a key role in bacterial interactions with their environment. Escherichia coli capsules were categorized as groups 1 through 4, each produced by a distinct mechanism. Etk and Etp are members of protein families required for the production of group 1 and group 4 capsules. These members function as a protein tyrosine kinase and protein tyrosine phosphatase, respectively. We show that Etp dephosphorylates Etk in vivo, and mutations rendering Etk or Etp catalytically inactive result in loss of group 4 capsule production, supporting the notion that cyclic phosphorylation and dephosphorylation of Etk is required for capsule formation. Notably, Etp also becomes tyrosine phosphorylated in vivo and catalyzes rapid auto-dephosphorylation. Further analysis identified Tyr121 as the phosphorylated residue of Etp. Etp containing Phe, Glu or Ala in place of Tyr121 retained phosphatase activity and catalyzed dephosphorylation of Etp and Etk. Although EtpY121E and EtpY121A still supported capsule formation, EtpY121F failed to do so. These results suggest that cycles of phosphorylation and dephosphorylation of Etp, as well as Etk, are involved in the formation of group 4 capsule, providing an additional regulatory layer to the complex control of capsule production. 相似文献
77.
Adi Tovin Shahar Alon Zohar Ben-Moshe Philipp Mracek Gad Vatine Nicholas S. Foulkes Jasmine Jacob-Hirsch Gideon Rechavi Reiko Toyama Steven L. Coon David C. Klein Eli Eisenberg Yoav Gothilf 《PLoS genetics》2012,8(12)
A wide variety of biochemical, physiological, and molecular processes are known to have daily rhythms driven by an endogenous circadian clock. While extensive research has greatly improved our understanding of the molecular mechanisms that constitute the circadian clock, the links between this clock and dependent processes have remained elusive. To address this gap in our knowledge, we have used RNA sequencing (RNA–seq) and DNA microarrays to systematically identify clock-controlled genes in the zebrafish pineal gland. In addition to a comprehensive view of the expression pattern of known clock components within this master clock tissue, this approach has revealed novel potential elements of the circadian timing system. We have implicated one rhythmically expressed gene, camk1gb, in connecting the clock with downstream physiology of the pineal gland. Remarkably, knockdown of camk1gb disrupts locomotor activity in the whole larva, even though it is predominantly expressed within the pineal gland. Therefore, it appears that camk1gb plays a role in linking the pineal master clock with the periphery. 相似文献
78.
Kim JS Romero R Tarca AL LaJeunesse C Han YM Kim MJ Suh YL Draghici S Mittal P Gotsch F Kusanovic JP Hassan S Kim CJ 《Journal of cellular and molecular medicine》2008,12(4):1317-1330
There is a difference in the susceptibility to inflammation between the umbilical vein (UV) and the umbilical arteries (UAs). This led us to hypothesize that there is an intrinsic difference in the pro-inflammatory response between UA and UV. Real-time quantitative RT-PCR and microarray analysis revealed higher expression of interleukin (IL)-1β and IL-8 mRNA in the UV and differential expression of 567 genes between the UA and UV associated with distinct biological processes, including the immune response. Differential expression of human leukocyte antigen (HLA)-DRA mRNA between the UA and UV was due to unexpected HLA-DR+ cells migrating via the umbilical vessels into Wharton's jelly, more frequently in the UV. A significant proportion of these cells co-expressed CD45 and type I pro-collagen, and acquired CD163 or α-smooth muscle actin immunoreactivity in Wharton's jelly. Migrating cells were also found in the chorionic and stem villous vessels. Furthermore, the extent of migration increased with progression of gestation, but diminished in intrauterine growth restriction (IUGR). The observations herein strongly suggest that circulating foetal fibrocytes, routing via umbilical and placental vessels, are a reservoir for key cellular subsets in the placenta. This study reports fibrocytes in the human umbilical cord and placenta for the first time, and a novel role for both circulating foetal cells and the umbilical vessels in placental development, which is deranged in IUGR. 相似文献
79.
80.
Adi B Brann Marianna Tcherpakov Ian M Williams Anthony H Futerman Mike Fainzilber 《The Journal of biological chemistry》2002,277(12):9812-9818
Binding of nerve growth factor (NGF) to the p75 neurotrophin receptor (p75) in cultured hippocampal neurons has been reported to cause seemingly contrasting effects, namely ceramide-dependent axonal outgrowth of freshly plated neurons, versus Jun kinase (Jnk)-dependent cell death in older neurons. We now show that the apoptotic effects of NGF in hippocampal neurons are observed only from the 2nd day of culture onward. This switch in the effect of NGF is correlated with an increase in p75 expression levels and increasing levels of ceramide generation as the cultures mature. NGF application to neuronal cultures from p75(exonIII-/-) mice had no effect on ceramide levels and did not affect neuronal viability. The neutral sphingomyelinase inhibitor, scyphostatin, inhibited NGF-induced ceramide generation and neuronal death, whereas hippocampal neurons cultured from acid sphingomyelinase(-/-) mice were as susceptible to NGF-induced death as wild type neurons. The acid ceramidase inhibitor, (1S,2R)-d-erythro-2-(N-myristoylamino)-1-phenyl-1-propanol, enhanced cell death, supporting a role for ceramide itself and not a downstream lipid metabolite. Finally, scyphostatin inhibited NGF-induced Jnk phosphorylation in hippocampal neurons. These data indicate an initiating role of ceramide generated by neutral sphingomyelinase in the diverse neuronal responses induced by binding of neurotrophins to p75. 相似文献