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991.
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993.
Fumihito Muro Shin Iimura Yoshiyuki Yoneda Jun Chiba Toshiyuki Watanabe Masaki Setoguchi Gensuke Takayama Mika Yokoyama Tohru Takashi Atsushi Nakayama Nobuo Machinaga 《Bioorganic & medicinal chemistry》2009,17(3):1232-1243
During the course of our study, it was revealed that the poor pharmacokinetic properties of a series of benzoic acid derivatives such as 1 should be attributed to the diphenylurea moiety. Thus, we replaced the diphenylurea moiety in 1 with a 2-(2-methylphenylamino)benzoxazole moiety which mimics the diphenylurea structure. However, this modification resulted in a significant decrease (3, IC50 = 19 nM) in VLA-4 inhibitory activity compared to 1 (IC50 = 1.6 nM). To address this discrepancy, we worked on optimization of the carboxylic acid moiety in compound 3. As a result, our efforts have led to the discovery of trans-4-substituted cyclohexanecarboxylic acid derivative 11b (IC50 = 2.8 nM) as a novel and potent VLA-4 antagonist. In addition, compound 11b exhibited favorable pharmacokinetic properties (CL = 3.3 ml/min/kg, F = 51%) in rats. 相似文献
994.
Teaching of parasitology to medical students in Japan 总被引:1,自引:0,他引:1
Kaneda Y 《Parasitology today (Personal ed.)》1999,15(1):40-41
995.
Isabelle Roszko Atsushi Sawada Lilianna Solnica-Krezel 《Seminars in cell & developmental biology》2009,20(8):986-997
Vertebrate gastrulation entails massive cell movements that establish and shape the germ layers. During gastrulation, the individual cell behaviors are strictly coordinated in time and space by various signaling pathways. These pathways instruct the cells about proliferation, shape, fate and migration into proper location. Convergence and extension (C&E) movements during vertebrate gastrulation play a major role in the shaping of the embryonic body. In vertebrates, the Wnt/Planar Cell Polarity (Wnt/PCP) pathway is a key regulator of C&E movements, essential for several polarized cell behaviors, including directed cell migration, and mediolateral and radial cell intercalation. However, the molecular mechanisms underlying the acquisition of Planar Cell Polarity by highly dynamic mesenchymal cells engaged in C&E are still not well understood. Here we review new evidence implicating the Wnt/PCP pathway in specific cell behaviors required for C&E during zebrafish gastrulation, in comparison to other vertebrates. We also discuss findings on the molecular regulation and the interaction of the Wnt/PCP pathway with other signaling pathways during gastrulation movements. 相似文献
996.
997.
Sugawara A Torigoe T Tamura Y Kamiguchi K Nemoto K Oguro H Sato N 《Cell stress & chaperones》2009,14(2):133-139
Polyamine compound deoxyspergualin (DSG) is a potent immunosuppressive agent that has been applied clinically for protecting
graft rejection and treatment of Wegener's granulomatosis. Though DSG can bind to heat-shock proteins (HSPs) in cells, its
mechanism of immunosuppressive action remains unknown. It is widely accepted that extracellular HSPs are capable of stimulating
dendritic cells (DC) through cell surface receptors, leading to DC activation and cytokine release. In this study, we examined
if DSG analogs could inhibit HSP70-induced DC activation. Bone marrow derived immature mouse DCs and peripheral blood mononuclear
cell-derived immature human DCs were generated and incubated with Alexa 488-labeled Hsp70 in the presence of methoxyDSG (Gus-1)
that had comparable HSP70-binding affinity to DSG or DSG analog GUS-7, which had much more reduced binding affinity for HSP70.
The binding of HSP70 to immature DCs was analyzed by laser microscopy and flow cytometry. HSP70-induced DC activation was
assessed by TNF-α release by enzyme-linked immunosorbent assay. Binding of Hsp70 to the cell surface of immature DCs was inhibited
under the presence of Gus-1, but not under the presence of Gus-7. Immature DCs were activated and released TNF-α by the stimulation
with HSP70 for 12 hours; however, the HSP70-induced TNF-α release was suppressed under the presence of Gus-1, and partially
suppressed under the presence of Gus-7. Similar results were observed when immature human DCs were stimulated under the same
conditions. Immunosuppressive mechanism of DSG may be explained, at least in part, by the inhibition of extracellular HSP70-DC
interaction and HSP70-induced activation of immature DCs.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
998.
Ryuji Yonekura Hiroki Yamanaka Atushi Ushimaru Kazuaki Matsui Kimiko Uchii Atsushi Maruyama 《Biological invasions》2009,11(6):1347-1355
Asymmetry in the competition abilities between invasive and native consumers can potentially influence the colonization success
by invasive species. We tested whether a subsidy of allochthonous prey enhanced an asymmetric competition between invasive
bluegill (Lepomis macrochirus) and two native cyprinid fish, that is, stone moroko (Pseudorasbora parva) and tamoroko (Gnathopogon elongatus elongatus). A field experiment was conducted using enclosures wherein the strength of interspecific competition and the presence/absence
of allochthonous prey were manipulated. The experiment revealed that allochthonous prey alleviated the limitation of fish
growths caused by a severe competition for aquatic prey resources. However, the importance of allochthonous prey differed
considerably between invasive bluegill and the two native cyprinids. Individual bluegills grew faster when the allochthonous
prey was supplied, whereas no difference in growth was observed in the two cyprinids whether or not allochthonous prey was
supplied. Interestingly, the importance of allochthonous prey on the total amount of bluegill growth varied depending on the
numerical abundance of native cyprinid competitors, and this importance increased when the native cyprinids were abundant.
These findings indicated that allochthonous prey provides an asymmetric growth benefit to invasive bluegills over the two
native cyprinids by alleviating asymmetrically the competition strength in a Japanese pond, especially under the conditions
of severe interspecific resource competition and a limitation in the utilization of in situ prey resources. 相似文献
999.
Yoshihiko Tsukada Atsushi Suetsugu Yosuke Osawa Hisataka Moriwaki 《Biochemical and biophysical research communications》2009,381(4):733-4088
Engelbreth-Holm-Swarm (EHS) gel has been reported to maintain the mature hepatocyte phenotypes in primary cultured hepatocytes. We investigated the effect of EHS gel on the differentiation of fetal liver cells, which contain stem/progenitor cells. The isolated fetal liver cells cultured on EHS gel formed a spherical shape and increased liver-specific gene expressions compared with cells cultured on collagen. The hepatic progenitor cells that were transplanted subcutaneously to BALB/c nude mice could survive and express hepatocyte marker alpha-fetoprotein when the cells were suspended with EHS gel. These findings demonstrate that EHS gel supports cytodifferentiation from immature progenitor cells to hepatocytes and maintain its differentiated phenotypes in vitro and in vivo. 相似文献
1000.
Shiori Kohno Yoshimi Nakano Moe Ishii Atsushi Baba 《Biochemical and biophysical research communications》2009,380(1):93-35256
Reelin is a secreted glycoprotein essential for normal brain development and function. In the extracellular milieu, Reelin is subject to specific cleavage at two (N-t and C-t) sites. The N-t cleavage of Reelin is implicated in psychiatric and Alzheimer’s diseases, but the molecular mechanism and physiological significance of this cleavage are not completely understood. Particularly, whether the N-t cleavage affects the signaling activity of Reelin remains controversial.Here, we show that the protease in charge of the N-t cleavage of Reelin requires the activity of certain proprotein convertase family for maturation and has strong affinity for heparin. By taking advantage of these observations, we for the first time succeeded in obtaining “Uncleaved” and “Completely Cleaved” Reelin proteins. The N-t cleavage splits Reelin into two distinct fragments and virtually abolishes its signaling activity. These findings provide an important biochemical basis for the function of Reelin proteolysis in brain development and function. 相似文献