全文获取类型
收费全文 | 15617篇 |
免费 | 551篇 |
国内免费 | 396篇 |
专业分类
16564篇 |
出版年
2024年 | 12篇 |
2023年 | 114篇 |
2022年 | 252篇 |
2021年 | 254篇 |
2020年 | 284篇 |
2019年 | 475篇 |
2018年 | 484篇 |
2017年 | 218篇 |
2016年 | 309篇 |
2015年 | 435篇 |
2014年 | 866篇 |
2013年 | 1013篇 |
2012年 | 542篇 |
2011年 | 979篇 |
2010年 | 667篇 |
2009年 | 787篇 |
2008年 | 815篇 |
2007年 | 889篇 |
2006年 | 826篇 |
2005年 | 752篇 |
2004年 | 635篇 |
2003年 | 589篇 |
2002年 | 494篇 |
2001年 | 355篇 |
2000年 | 320篇 |
1999年 | 337篇 |
1998年 | 367篇 |
1997年 | 282篇 |
1996年 | 255篇 |
1995年 | 260篇 |
1994年 | 221篇 |
1993年 | 166篇 |
1992年 | 154篇 |
1991年 | 127篇 |
1990年 | 113篇 |
1989年 | 101篇 |
1988年 | 88篇 |
1987年 | 82篇 |
1986年 | 46篇 |
1985年 | 90篇 |
1984年 | 128篇 |
1983年 | 90篇 |
1982年 | 78篇 |
1981年 | 49篇 |
1980年 | 46篇 |
1979年 | 35篇 |
1978年 | 19篇 |
1977年 | 14篇 |
1976年 | 13篇 |
1974年 | 14篇 |
排序方式: 共有10000条查询结果,搜索用时 0 毫秒
101.
102.
溴化十烷基三甲铵对肌酸激酶的变性及复性 总被引:5,自引:1,他引:5
测定了溴化十烷基三甲铵(C_(10)H_(21)N(CH_3)_3Br;记为C_(10)NM_3)对肌酸激酶(Creatine Kinase;记为C.K.)的活力及构象的影响,以及变性后C.K.的复性。实验结果表明:C_(10)NM_3对C.K.有很强的变性能力,在0.06M时,就可以使C.K.完全失活;在0.08M时,就可使C.K.内部的6个巯基有4个暴露出来;与SDS变性剂不同,C.K.在高浓度的C_(10)NM_3中变性以后,直接冲稀时就可以完全复性。FTIR以及CD等实验方法证明,尽管C_(10)NM_3能使C.K.的构象发生明显变化,但C.K.的二级结构几乎不受C_(10)NM_3的影响。 相似文献
103.
A. A. Galoyan B. Ya. Gurvits L. A. Shuvalova Michael T. Davis John E. Shively Terry D. Lee 《Neurochemical research》1992,17(8):773-777
A new class of stimulators of basal activity of a number of calmodulin-dependent enzymes have been previously isolated from bovine hypothalamus. One of these stimulators, denoted as C3, has been purified to homogeneity by reverse phase HPLC and tentatively identified as thymosin 4 (1–39) by mass spectrometry and Edman microsequence analysis. The stimulating effect of C3 on rabbit skeletal muscle MLCK basal activity was compared with that of thymosin 1 and thymosin 4 (16–38). Evidence is presented that all the indicated compounds are Ca2+-independent high-affinity MLCK stimulators. The potency of the stimulators in activating the enzyme was: C3>4>(CaM+Ca2+>1.This revised version was published online in June 2005 with corrections to the author name Gurvits. 相似文献
104.
Sajal Chakraborti Animesh Chowdhury Pulak Kar Partha Das Soni Shaikh Soumitra Roy Tapati Chakraborti 《Archives of biochemistry and biophysics》2009,487(2):123-130
Treatment of bovine pulmonary smooth muscle cells with the TxA2 mimetic, U46619 stimulated [Ca2+]i, which was inhibited upon pretreatment with apocynin (NADPH oxidase inhibitor). Pretreatment with cromakalim (KV channel opener) or nifedepine (L-VOCC inhibitor) inhibited U46619 induced increase in [Ca2+]i, indicating a role of KV-LVOCC axis in this scenario. Neither cromakalim nor nifedepine inhibited U46619 induced increase in NADPH oxidase activity, suggesting that the NADPH oxidase activation is proximal to the KV-LVOCC axis in the cells. Pretreatment with calphostin C (PKC inhibitor) markedly reduced U46619 induced increase in NADPH oxidase activity and [Ca2+]i in the cells. Calphostin C pretreatment also markedly reduced p47phox phosphorylation and translocation to the membrane and association with p22phox, a component of Cyt.b558 of NADPH oxidase in the membrane. Overall, PKC plays an important role in NADPH oxidase derived O2−-mediated regulation of KV-LVOCC axis leading to an increase in [Ca2+]i by U46619 in the cells. 相似文献
105.
Rui-Fang Li Xin-Xin Wang Liu Wu Li Huang Qi-Jian Qin Jia-Li Yao Guang-Tao Lu Ji-Liang Tang 《Molecular Plant Pathology》2020,21(3):360-375
Xanthomonas campestris pv. campestris (Xcc) controls virulence and plant infection mechanisms via the activity of the sensor kinase and response regulator pair HpaS/hypersensitive response and pathogenicity G (HrpG). Detailed analysis of the regulatory role of HpaS has suggested the occurrence of further regulators besides HrpG. Here we used in vitro and in vivo approaches to identify the orphan response regulator VemR as another partner of HpaS and to characterize relevant interactions between components of this signalling system. Bacterial two-hybrid and protein pull-down assays revealed that HpaS physically interacts with VemR. Phos-tag SDS-PAGE analysis showed that mutation in hpaS reduced markedly the phosphorylation of VemR in vivo. Mutation analysis reveals that HpaS and VemR contribute to the regulation of motility and this relationship appears to be epistatic. Additionally, we show that VemR control of Xcc motility is due in part to its ability to interact and bind to the flagellum rotor protein FliM. Taken together, the findings describe the unrecognized regulatory role of sensor kinase HpaS and orphan response regulator VemR in the control of motility in Xcc and contribute to the understanding of the complex regulatory mechanisms used by Xcc during plant infection. 相似文献
106.
Kimio Takeuchi Yuki Morizane Cynthia Kamami-Levy Jun Suzuki Maki Kayama Wenyi Cai Joan W. Miller Demetrios G. Vavvas 《The Journal of biological chemistry》2013,288(28):20581-20591
Caveolin-1 is the primary structural component of endothelial caveolae that is essential for transcellular trafficking of albumin and is also a critical scaffolding protein that regulates the activity of signaling molecules in caveolae. Phosphorylation of caveolin-1 plays a fundamental role in the mechanism of oxidant-induced vascular hyper permeability. However, the regulatory mechanism of caveolin-1 phosphorylation remains unclear. Here we identify a previously unexpected role for AMPK in inhibition of caveolin-1 phosphorylation under oxidative stress. A pharmacological activator of AMPK, 5-amino-4-imidazole carboxamide riboside (AICAR), inhibited oxidative stress-induced phosphorylation of both caveolin-1 and c-Abl, which is the major kinase of caveolin-1, and endocytosis of albumin in human umbilical vein endothelial cell. These effects were abolished by treatment with two specific inhibitors of AICAR, dipyridamole, and 5-iodotubericidin. Consistently, knockdown of the catalytic AMPKα subunit by siRNA abolished the inhibitory effect of AICAR on oxidant-induced phosphorylation of both caveolin-1 and c-Abl. Pretreatment with specific c-Abl inhibitor, imatinib mesylate, and knock down of c-Abl significantly decreased the caveolin-1 phosphorylation after H2O2 exposure and abolished the inhibitory effect of AICAR on the caveolin-1 phosphorylation. Interestingly, knockdown of Prdx-1, an antioxidant enzyme associated with c-Abl, increased phosphorylation of both caveolin-1 and c-Abl and abolished the inhibitory effect of AICAR on the caveolin-1 phosphorylation. Furthermore, co-immunoprecipitation experiment showed that AICAR suppressed the oxidant-induced dissociation between c-Abl and Prdx1. Overall, our results suggest that activation of AMPK inhibits oxidative stress-induced caveolin-1 phosphorylation and endocytosis, and this effect is mediated in part by stabilizing the interaction between c-Abl and Prdx-1. 相似文献
107.
High-affinity L-glutamate (GLU) transport is an important regulator of excitatory amino acid (EAA) concentrations in brain extracellular fluid and may play a key role in excitatory synaptic transmission. In view of evidence that EAA transporters (EAAT) are heterogenous and contain consensus sites for phosphorylation, this investigation was undertaken to contrast the effects of transporter phosphorylation in fractions derived from glia and neurons (synaptosomes) of the adult rat forebrain. Treatment with phorbol-12,13-dibutyrate (PDBu), an activator of protein kinase C (PKC), increased the maximal rate of GLU transport in glial plasmalemmal vesicles by greater than 50 percent (237 ± 18 vs. 365 ± 27 pmol/mg protein/90s, p < 0.05) but caused no change in synaptosomes. The effect by PDBu was concentration and time-dependent and was inhibited completely by the PKC inhibitor calphostin C. Inhibition of serine-threonine phosphoprotein phosphatases with okadaic acid produced similar effects which were not additive with PDBu. Together, these results demonstrate that glial EAAT can be regulated by multiple phosphorylation processes. 相似文献
108.
Rat liver casein kinase TS (Ck-TS) having quarternary structure α2β2, autophosphorylates at its 25 kDa, β-subunits, incorporating up to 1.2 mol P/mol enzyme. According to their effects on the autophosphorylation pattern the effectors of Ck-TS activity can be grouped into 3 classes: (i) inhibitors, like heparin, which also prevent the autophosphorylation of the β-subunit; (ii) stimulators possessing several amino groups (like spermine) which increase the autophosphorylation at the β-subunit; (iii) stimulators possessing several guanido groups, like protamines and related peptides, which prevent the phosphorylation of the β-subunit, while promoting the autophosphorylation of the 38 kDa α-subunit. In the presence of such polyarginyl effectors the 130 kDa Ck-TS is converted into forms with higher sedimentation coefficient. 相似文献
109.
Protein serine/threonine kinase casein kinase 2 (CK2) is a key player in cell growth and proliferation but is also a potent suppressor of apoptosis. CK2 has been found to be dysregulated in all the cancers that have been examined, including prostate cancer. Investigations of CK2 signaling in the prostate were originally initiated in this laboratory, and these studies have identified significant functional activities of CK2 in relation to normal prostate growth and to the pathobiology of androgen-dependent and -independent prostate cancer. We present a brief overview of these developments in the context of prostate biology. An important outcome of these studies is the emerging concept that CK2 can be effectively targeted for cancer therapy. 相似文献
110.
Our understanding of the evolution of the insulin signaling pathway (ISP) is still incomplete. One intriguing unanswered question is the explanation of the emergence of the glucostatic role of insulin in mammals. To find out whether this is due to the development of new sets of signaling transduction elements in these organisms, or to the establishment of new interactions between pre-existing proteins, we rebuilt putative orthologous ISPs in 17 eukaryotic organisms. Then, we computed the conservation of orthologous ISPs at different levels, from sequence similarity of orthologous proteins to co-evolution of interacting domains. We found that the emergence of glucostatic role in mammals can neither be explained by the development of new sets of signaling elements, nor by the establishment of new interactions between pre-existing proteins. The comparison of orthologous IRS molecules indicates that only in mammals have they acquired their complete functionality as efficient recruiters of effector sub-pathways. 相似文献