全文获取类型
收费全文 | 15910篇 |
免费 | 586篇 |
国内免费 | 389篇 |
出版年
2023年 | 119篇 |
2022年 | 252篇 |
2021年 | 288篇 |
2020年 | 305篇 |
2019年 | 527篇 |
2018年 | 513篇 |
2017年 | 233篇 |
2016年 | 323篇 |
2015年 | 450篇 |
2014年 | 901篇 |
2013年 | 1078篇 |
2012年 | 567篇 |
2011年 | 983篇 |
2010年 | 689篇 |
2009年 | 801篇 |
2008年 | 821篇 |
2007年 | 899篇 |
2006年 | 833篇 |
2005年 | 763篇 |
2004年 | 629篇 |
2003年 | 590篇 |
2002年 | 495篇 |
2001年 | 366篇 |
2000年 | 320篇 |
1999年 | 339篇 |
1998年 | 364篇 |
1997年 | 290篇 |
1996年 | 256篇 |
1995年 | 256篇 |
1994年 | 219篇 |
1993年 | 168篇 |
1992年 | 154篇 |
1991年 | 130篇 |
1990年 | 109篇 |
1989年 | 89篇 |
1988年 | 84篇 |
1987年 | 78篇 |
1986年 | 41篇 |
1985年 | 85篇 |
1984年 | 122篇 |
1983年 | 83篇 |
1982年 | 72篇 |
1981年 | 45篇 |
1980年 | 40篇 |
1979年 | 33篇 |
1978年 | 15篇 |
1977年 | 16篇 |
1976年 | 10篇 |
1975年 | 10篇 |
1974年 | 12篇 |
排序方式: 共有10000条查询结果,搜索用时 421 毫秒
141.
Abstract: We have shown previously that a neurofilament (NF)-associated kinase (NFAK) extracted from chicken NF preparations phosphorylates selectively the middle molecular mass NF subunit (NF-M). Here we show that the major kinase activity in NFAK is indistinguishable from enzymes of the casein kinase I (CKI) family based on the following criteria: (1) inhibition of NFAK phosphorylation by the selective CKI inhibitor CKI-7, (2) the similarity in substrate specificity of NFAK and authentic CKI, (3) the correspondence of two-dimensional phosphopeptide maps of NF-M phosphorylated in vitro by NFAK with those generated by CKI under similar conditions, and (4) immunological cross-reactivity of NFAK with an antibody raised against CKI. We have also identified Ser502 , Ser528 , and Ser536 as phosphorylation sites by NFAK/CKI in vitro, each of which is also phosphorylated in vivo. All three serines are found in peptides with CKI phosphorylation consensus sequences, and Ser528 and Ser536 and flanking amino acids are highly conserved in higher vertebrate NF-M sequences. Neither Ser502 nor Ser536 has been identified previously as NF-M phosphorylation sites. 相似文献
142.
Abstract: To determine whether protein kinase C (PKC) mediates release of peptides from sensory neurons, we examined the effects of altering PKC activity on resting and evoked release of substance P (SP) and calcitonin gene-related peptide (CGRP). Exposing rat sensory neurons in culture to 10 or 50 n M phorbol 12,13-dibutyrate (PDBu) significantly increased SP and CGRP release at least 10-fold above resting levels, whereas the inactive 4α-PDBu analogue at 100 n M had no effect on release. Furthermore, 100 n M bradykinin increased peptide release approximately fivefold. Down-regulation of PKC significantly attenuated the release of peptides evoked by either PDBu or bradykinin. PDBu at 1 n M or 1-oleoyl-2-acetyl- sn -glycerol at 50 µ M did not alter resting release of peptides, but augmented potassium- and capsaicin-stimulated release of both SP and CGRP approximately twofold. This sensitizing action of PKC activators on peptide release was significantly reduced by PKC down-regulation or by pretreating cultures with 10 n M staurosporine. These results establish that activation of PKC is important in the regulation of peptide release from sensory neurons. The PKC-induced enhancement of peptide release may be a mechanism underlying the neuronal sensitization that produces hyperalgesia. 相似文献
143.
144.
Protein Tyrosine Kinase-Mediated Potentiation of Currents from Cloned NMDA Receptors 总被引:13,自引:8,他引:5
Abstract: Although serine/threonine phosphorylation has been more commonly recognized as a mechanism to modulate the function of ion channels and receptors, tyrosine phosphorylation is under increasing scrutiny. An important subtype of glutamate receptor, the NMDA receptor, is shown to be regulated by insulin via protein tyrosine kinase (PTK). NMDA currents through cloned receptors are potentiated by insulin in a subunit-specific manner. The insulin-mediated potentiation of NMDA current is diminished by inhibitors of PTKs. At least one exogenous cytosolic PTK, pp60c- src , is also able to potentiate NMDA current. Because later application of PTK inhibitors can reverse the seemingly stable insulin-mediated potentiation of NMDA current, it appears that tyrosine residues responsible for potentiation are continually rephosphorylated by some long-term PTK activity that was induced via insulin treatment. 相似文献
145.
Hidetaka Kosako Yukiko Gotoh Eisuke Nishida 《Development, growth & differentiation》1996,38(6):577-582
Mitogen-activated protein kinase (MAPK) was originally identified as a serine/threonine protein kinase that is rapidly activated in response to various growth factors and tumor promoters in mammalian cultured cells. The kinase cascade including MAPK and its direct activator, MAPK kinase (MAPKK), is now believed to transmit various extracellular signals into their intracellular targets in eukaryotic cells. It has been reported that activation of MAPKK and MAPK occurs during the meiotic maturation of oocytes in several species, including Xenopus laevis . Studies with neutralizing antibodies against MAPKK, MAPK phosphatases and constitutively active MAPKK or MAPK have revealed a crucial role of the MAPKK/MAPK cascade in a number of developmental processes in Xenopus oocytes and embryos. 相似文献
146.
Reconstituted Na+,K+-ATPase from either pig kidney or shark rectal glands was phosphorylated by cAMP dependent protein kinase, PKA. The stoichiometry was 0.9 mole Pi/mole -subunit in the pig kidney enzyme and 0.2 mol Pi/mol -subunit in the shark enzyme. In shark Na+,K+-ATPase PKA phosphorylation increased the maximum hydrolytic activity for cytoplasmic Na+ activation and extracellular K+ activation without affecting the apparent Km values. In contrast, no significant functional effect after PKA phosphorylation was observed in pig kidney Na+,K+-ATPase. 相似文献
147.
Abstract: Previous work has shown that nerve growth factor (NGF) stimulates the phosphorylation of the ribosomal protein S6 in PC12 cells. In this study, we show that S6 kinase activity is also present in purified PC12 cell nuclei. This activity was increased by treatment of the cells with NGF and, to a lesser extent, by treatment with epidermal growth factor. The NGF-stimulated activity was obtained from nuclear extracts and some of its characteristics described. The increase in activity was prevented by treatment of the cells with rapamycin or with wortmannin, and the overall activity could be precipitated by antibodies directed against the p85S6K . These data indicate that p85S6K is the NGF-stimulated S6 kinase in PC12 cell nuclei. The presence of S6 protein in the nucleus of PC12 cells has been confirmed and evidence is presented that suggests that it is identical to a protein called SMP reported some years ago. 相似文献
148.
In yeast the GCN2 kinase mediates translational control ofGCN4 by phosphorylating the subunit of eIF-2 in response to extracellular amino acid limitation. Although phosphorylation of eIF-2 has been shown to inhibit global protein synthesis, amino acid starvation results in a specific activation effect onGCN4 mRNA translation. Under the same conditions, translation of other mRNAs appears only slightly affected. The mechanism responsible for the observed selectivity of the GCN2 kinase is not clear. Here, we present genetic evidence that suggests that locally restricted action of the GCN2 kinase facilitatesGCN4-specific translational regulation. 相似文献
149.
Masashi Yamada Toshihiko Ikeuchi Saburo Aimoto Dr. Hiroshi Hatanaka 《Neurochemical research》1996,21(7):815-822
PC12h-R cell, a subclone of PC12 cells, exhibited a neuron-like phenotype, including neurite outgrowth and increased acetylcholinesterase
activity, in response to epidermal growth factor (EGF) as well as nerve growth factor (NGF). We examined the mechanism by
which EGF induced the neuronal differentiation in PC12h-R cells. The EGF-induced neuronal differentiation of PC12h-R cells
was not blocked by K252a, whereas that induced by NGF was. EGF induced sustained tyrosine phosphorylation of the EGF receptor
in PC12h-R cells, but not in the parent PC12h cells, which do not show neuronal differentiation in response to EGF. In addition,
the rate of EGF-induced down-regulation of the EGF receptor in PC12h-R cells was decreased compared with that in PC12h cells.
Furthermore, we found that the duration of EGF-induced tyrosine phosphorylation of the EGF receptor in PC12h-R cells was similar
to that of NGF-induced tyrosine phosphorylation of p140
trkA in PC12h cells. The EGF-induced phosphorylation of the EGF receptor in PC12h cells was less sustained than that of p140
trkA by NGF in PC12h cells. These findings suggested that the EGF-induced neuronal differentiation of PC12h-R cells is due to
the sustained activation of the EGF receptor, resulting from the decreased down-regulation of the EGF receptor and that the
duration of the receptor tyrosine kinase activity determines the cellular responses of PC12 cells. We concluded that sustained
activation of the receptor tyrosine kinase induces neuronal differentiation, although transient activation promotes proliferation
of PC12 cells.
Special issue dedicated to Dr. Hans Thoenen. 相似文献
150.
丝裂素活化蛋白激酶参与内皮素刺激的兔主动脉平滑肌细胞增生 总被引:11,自引:1,他引:10
内皮素(endothelin,ET)是已知的体内活性最强的缩血管物质,其缩血管作用由G蛋白偶联受体所介导。但ET强大的促血管平滑肌细胞(VSMC)增生效应的机理尚未完全阐明。本研究选用培养的兔胸主动脉VSMC,探讨丝裂素活化蛋白激酶(MAPK)在ET促细胞增生中的作用。结果表明:ET-1呈时间和浓度依赖性地促进细胞摄取 ̄3H-TdR和激活MAPK,此作用可被蛋白激酶C(proteinkinaseC,PKC)抑制剂Staurosporine(STP),H-7和ET_A受体拮抗剂BQ123所抑制,但不被酪氨酸激酶抑制剂HerbimycinA(Herb)所抑制,用PKC激动剂PMA(Phorbolmyristateacetate)预处理VSMC,使其PKC活性下调,可显著减弱ET-1对MAPK的激活能力。本结果提示:(1)MAPK参与ET-1所致的VSMC增生;(2)ET-1促细胞增生与激活MAPK的作用是由ET_A受体和PKC介导的。 相似文献