全文获取类型
收费全文 | 2241篇 |
免费 | 227篇 |
出版年
2021年 | 31篇 |
2020年 | 19篇 |
2019年 | 28篇 |
2018年 | 26篇 |
2017年 | 25篇 |
2016年 | 31篇 |
2015年 | 57篇 |
2014年 | 75篇 |
2013年 | 86篇 |
2012年 | 100篇 |
2011年 | 113篇 |
2010年 | 68篇 |
2009年 | 66篇 |
2008年 | 93篇 |
2007年 | 86篇 |
2006年 | 72篇 |
2005年 | 83篇 |
2004年 | 87篇 |
2003年 | 81篇 |
2002年 | 82篇 |
2001年 | 70篇 |
2000年 | 92篇 |
1999年 | 75篇 |
1998年 | 39篇 |
1997年 | 30篇 |
1996年 | 39篇 |
1995年 | 25篇 |
1994年 | 31篇 |
1993年 | 28篇 |
1992年 | 44篇 |
1991年 | 50篇 |
1990年 | 44篇 |
1989年 | 25篇 |
1988年 | 51篇 |
1987年 | 38篇 |
1986年 | 42篇 |
1985年 | 33篇 |
1984年 | 34篇 |
1983年 | 18篇 |
1982年 | 27篇 |
1981年 | 25篇 |
1979年 | 21篇 |
1978年 | 23篇 |
1977年 | 21篇 |
1975年 | 24篇 |
1974年 | 21篇 |
1973年 | 18篇 |
1972年 | 16篇 |
1971年 | 22篇 |
1969年 | 19篇 |
排序方式: 共有2468条查询结果,搜索用时 46 毫秒
1.
Elevated levels of intracellular calcium are a major cause of myocardial dysfunction. To find possible mediators of the deregulated calcium we searched for EF-hand calcium-binding proteins of the S100 family. By PCR technology we identified three members of the S100 protein family (S100 alpha, CACY, and CAPL) in the human heart. We cloned the corresponding cDNAs and examined their expression levels in various human tissues by Northern blot analysis. All three proteins are expressed at high levels in the human heart. Whereas CACY and CAPL mRNAs are expressed ubiquitously, S100 alpha mRNA is restricted to heart, skeletal muscle, and brain. Interestingly, the expression pattern of S100 alpha, CACY, and CAPL in human tissues differs significantly from that in rodent tissues. 相似文献
2.
S-Protein/vitronectin is a serum glycoprotein that inhibits the lytic activity of the membrane attack complex of complement, i.e., of the complex including the proteins C5b, C6, C7, C8, and C9n. We show that intact S-protein/vitronectin or its cyanogen bromide generated fragments also inhibit the hemolysis mediated by perforin from cytotoxic T-cells at 45 and 11 microM, respectively. The glycosaminoglycan binding site of S-protein/vitronectin is responsible for the inhibition, since a synthetic peptide corresponding to a part of this highly basic domain (amino acid residues 348-360) inhibits complement- as well as perforin-mediated cytolysis. In the case of C9, the synthetic peptide binds to the acidic residues occurring in its N-terminal cysteine-rich domain (residues 101-111). Antibodies raised against this particular segment react 25-fold better with the polymerized form of C9 as compared with its monomeric form, indicating that this site becomes exposed only upon the hydrophilic-amphiphilic transition of C9. Since the cysteine-rich domain of C9 has been shown to be highly conserved in C6, C7, and C8 as well as in perforin, the inhibition of the lytic activities of these molecules by S-protein/vitronectin or by peptides corresponding to its heparin binding site may be explained by a similar mechanism. 相似文献
3.
Reversible succinate dehydrogenase (SDH) activities have been ubiquitously detected in organisms from the three domains of life. They represent constituents either of respiratory complexes II in aerobes, or of fumarate dehydrogenase complexes in anaerobes. The present review gives a survey on archaeal succinate:quinone oxidoreductases (SQRs) analyzed so far. Though some of these could be studied in detail enzymologically and spectroscopically, the existence of others has been deduced only from published genome sequences. Interestingly, two groups of enzyme complexes can be distinguished in Archaea. One group resembles the properties of SDHs known from bacteria and mitochondria. The other represents a novel class with an unusual iron-sulfur cluster in subunit B and atypical sequence motifs in subunit C which may influence electron transport mechanisms and pathways. This novel class of SQRs is discussed in comparison to the so-called 'classical' complexes. A phylogenetic analysis is presented suggesting a co-evolution of the flavoprotein-binding subunit A and subunit B containing the three iron-sulfur clusters. 相似文献
4.
V. v. Borbás P. L. Wiedermann Franz Hüfer E. Hackel 《Plant Systematics and Evolution》1890,40(11):427-428
Ohne Zusammenfassung 相似文献
5.
6.
7.
Wounding of quiescent white potato tuber tissue enhances chromatin-boundprotein phosphokinase activity, which exhibits two distinctphases during wound-healing. A moderate activation of the enzymesup to 20 hr after injury is followed by a dramatic increasein activity with a peak at 50 hr. This time-course resemblesthat of chromatinbound DNA-dependent RNA polymerase with a peakin activity at about 48 hr after wounding. The kinases phosphorylateendogenous proteins as well as added histones, phosvitin andcasein. The incorporated phosphate is stable under standardassay conditions, indicating the absence of protein phosphatases.Sensitivity of the incorporated phosphate toward trypsin andalkali, but not DNase, RNase, hydroxylamine or succinic acidpoints to seryl- and threonyl-bonds and proteins as acceptormolecules. Kinases from resting tissues are only weakly stimulatedeven by 100 mM MgCl2, those from wounded tissues exhibit pronouncedMg$$-optima at 510 mM with endogenous proteins, phosvitinand casein and 50 mM MgCl2 with histones. Wounding also increasesthe sensitivity of the kinases toward p-hydroxymercuribenzoate. Chromatin preparations from both resting and wounded tissuescontain about 40 protein bands after polyacrylamide disc gelelectrophoresis. In vitro phosphorylation of these proteinsin chromatin from quiescent tissues is comparably low and uniform.Wounding induces changes in the protein and phosphorylationpattern with a general enhancement of phosphorylative capacityand preferential phosphorylation of low molecular weight proteins. (Received August 10, 1981; Accepted November 18, 1981) 相似文献
8.
Michaela Ludolphs Daniela Schneeberger Tolga Soykan Jonas Sch?fer Theofilos Papadopoulos Nils Brose Hermann Schindelin Claudia Steinem 《The Journal of biological chemistry》2016,291(1):244-254
The regulatory protein collybistin (CB) recruits the receptor-scaffolding protein gephyrin to mammalian inhibitory glycinergic and GABAergic postsynaptic membranes in nerve cells. CB is tethered to the membrane via phosphoinositides. We developed an in vitro assay based on solid-supported 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine membranes doped with different phosphoinositides on silicon/silicon dioxide substrates to quantify the binding of various CB2 constructs using reflectometric interference spectroscopy. Based on adsorption isotherms, we obtained dissociation constants and binding capacities of the membranes. Our results show that full-length CB2 harboring the N-terminal Src homology 3 (SH3) domain (CB2SH3+) adopts a closed and autoinhibited conformation that largely prevents membrane binding. This autoinhibition is relieved upon introduction of the W24A/E262A mutation, which conformationally “opens” CB2SH3+ and allows the pleckstrin homology domain to properly bind lipids depending on the phosphoinositide species with a preference for phosphatidylinositol 3-monophosphate and phosphatidylinositol 4-monophosphate. This type of membrane tethering under the control of the release of the SH3 domain of CB is essential for regulating gephyrin clustering. 相似文献
9.
Reinhard Told Stefan Palkovits Helmuth Haslacher Sophie Frantal Doreen Schmidl Agnes Boltz Michael Lasta Semira Kaya René M. Werkmeister Gerhard Garh?fer Leopold Schmetterer 《PloS one》2013,8(4)
A common polymorphism in the complement factor H gene (rs1061170, Y402H) is associated with a high risk of age-related macular degeneration (AMD). In the present study we hypothesized that healthy young subjects homozygous for the high-risk haplotype (CC) show abnormal choroidal blood flow (ChBF) regulation decades before potentially developing the disease. A total of 100 healthy young subjects were included in the present study, of which 4 subjects were excluded due to problems with genotyping or blood flow measurements. ChBF was measured continuously using laser Doppler flowmetry while the subjects performed isometric exercise (squatting) for 6 minutes. The increase in ChBF was less pronounced than the response in ocular perfusion pressure (OPP), indicating for some degree of choroidal blood flow regulation. Eighteen subjects were homozygous for C, 47 subjects were homozygous for T and 31 subjects were heterozygous (CT). The increase in OPP during isometric exercise was not different between groups. By contrast the increase in ChBF was more pronounced in subjects homozygous for the high risk C allele (p = 0.041). This was also evident from the pressure/flow relationship, where the increase in ChBF in homozygous C carriers started at lower OPPs as compared to the other groups. Our data indicate that the regulation of ChBF is abnormal in rs1061170 CC carriers. So far this polymorphism has been linked to age related macular degeneration (AMD) mainly via inflammatory pathways associated with the complement system dysfunction. Our results indicate that it could also be related to vascular factors that have been implicated in AMD pathogenesis. 相似文献
10.