全文获取类型
收费全文 | 2357篇 |
免费 | 147篇 |
国内免费 | 3篇 |
出版年
2023年 | 15篇 |
2022年 | 18篇 |
2021年 | 37篇 |
2020年 | 30篇 |
2019年 | 32篇 |
2018年 | 39篇 |
2017年 | 30篇 |
2016年 | 80篇 |
2015年 | 113篇 |
2014年 | 141篇 |
2013年 | 162篇 |
2012年 | 194篇 |
2011年 | 209篇 |
2010年 | 108篇 |
2009年 | 103篇 |
2008年 | 143篇 |
2007年 | 152篇 |
2006年 | 132篇 |
2005年 | 128篇 |
2004年 | 78篇 |
2003年 | 114篇 |
2002年 | 87篇 |
2001年 | 9篇 |
2000年 | 13篇 |
1999年 | 9篇 |
1998年 | 20篇 |
1997年 | 19篇 |
1996年 | 12篇 |
1995年 | 11篇 |
1994年 | 9篇 |
1993年 | 19篇 |
1992年 | 15篇 |
1991年 | 17篇 |
1990年 | 14篇 |
1989年 | 14篇 |
1988年 | 14篇 |
1987年 | 12篇 |
1986年 | 12篇 |
1985年 | 11篇 |
1984年 | 10篇 |
1983年 | 13篇 |
1982年 | 13篇 |
1981年 | 7篇 |
1980年 | 10篇 |
1979年 | 17篇 |
1978年 | 11篇 |
1977年 | 7篇 |
1975年 | 6篇 |
1971年 | 5篇 |
1969年 | 6篇 |
排序方式: 共有2507条查询结果,搜索用时 234 毫秒
991.
Ragnar Kinzelbach und Jochen Martens 《Journal of Ornithology》1964,105(2):137-148
Zusammenfassung Eine kritische Untersuchung aller Nachrichten über das Auftreten der Beutelmeise im Oberrheingebiet ergab, daß dieser Vogel hier nur in gewissen Zeitabständen auftritt (um 1820, 1880–1900, 1934/35, seit 1950). Diese Vorstöße wurden homologisiert mit Übervermehrung östlicher Populationen, die dann auf ihrem Zug das Oberrheingebiet berühren. Dabei kommt es gelegentlich zum Übersommern einzelner Tiere, wobei öfter — wohl unverpaarte — Männchen Nester zu bauen beginnen. Doch dürften auch vereinzelt erfolgreiche Bruten stattgefunden haben, wiewohl ein exakter Nachweis aus dem eigentlichen Oberrheingebiet noch aussteht. 相似文献
992.
Hormone-induced rise in cytosolic Ca2+ in axolotl hepatocytes: properties of the Ca2+ influx channel 总被引:1,自引:0,他引:1
Calcium entry in nonexcitable cells occurs throughCa2+-selective channels activatedsecondarily to store depletion and/or through receptor- orsecond messenger-operated channels. In amphibian liver, hormones thatstimulate the production of adenosine 3',5'-cyclic monophosphate (cAMP) also regulate the opening of an ion gate in theplasma membrane, which allows a noncapacitative inflow ofCa2+. To characterize thisCa2+ channel, we studied theeffects of inhibitors of voltage-dependent Ca2+ channels and of nonselectivecation channels on 8-bromoadenosine 3',5'-cyclicmonophosphate (8-BrcAMP)-dependentCa2+ entry in single axolotlhepatocytes. Ca2+ entry provokedby 8-BrcAMP in the presence of physiologicalCa2+ followed first-order kinetics(apparent Michaelis constant = 43 µM at the cellsurface). Maximal values of cytosolicCa2+ (increment ~300%) werereached within 15 s, and the effect was transient (half time of 56 s).We report a strong inhibition of cAMP-dependentCa2+ entry by nifedipine[half-maximal inhibitory concentration(IC50) = 0.8 µM], byverapamil (IC50 = 22 µM), andby SK&F-96365 (IC50 = 1.8 µM).Depolarizing concentrations of K+were without effect. Gadolinium and the anti-inflammatory compound niflumate, both inhibitors of nonselective cation channels, suppressed Ca2+ influx. This "profile"indicates a novel mechanism ofCa2+ entry in nonexcitable cells. 相似文献
993.
Jochen Walz Dieter Typke Michael Nitsch Abraham J. Koster Reiner Hegerl Wolfgang Baumeister 《Journal of structural biology》1997,120(3):387-395
From 3-D reconstructions of automatically recorded tilt series of ice-embedded macromolecules, several hundred 3-D images of single particles can be extracted. Here we describe correlation-based techniques to align the particles with respect to translation and orientation in 3-D and the calculation of an averaged reconstruction after application of the correct weighting function to the particle projections. Multivariate statistical analysis and classification are applied to the set of three-dimensionally reconstructed particles to investigate interimage variations on the 3-D level. 相似文献
994.
Thomas Brinkmann Jochen Schäfers Lutz Gürtler Hiroshi Kido Yasuharu Niwa Nobuhiko Katunuma Harald Tschesche 《The protein journal》1997,16(6):651-660
The serine esterase TL2 from human T4+ lymphocytes is a binding component to HIV-1 glycoprotein gp120 and seems to play a role in the HIV-1 infection mechanism. Recombinant variants of the Kunitz-type serine proteinase inhibitor aprotinin were investigated for their ability to inhibit tryptase TL2 and the binding of gp120 to this enzyme. Furthermore, the viral replication of HIV-1 was investigated in H9 cell cultures under the influence of recombinant aprotinin and bikunin variants. In contrast to native aprotinin, the recombinant variant [Arg15, Phe17, Glu52]aprotinin with a reactive-site sequence homologous to the V3 loop of HIV-1 gp120 showed a specific inhibition of tryptase TL2 (>80%). However, the [Leu15, Phe17, Glu52]aprotinin variant with hydrophobic subsites was the most potent inhibitor of the binding of gp120 to tryptase TL2 (68%). Our results show that the enzyme activity of purified tryptase TL2 is inhibited not only by variants with basic amino acids, but also those with hydrophobic residues in the reactive-site region. Therefore, tryptase TL2 is not a typical trypsin-like or chymotrypsin-like protease. Investigations on inhibition of HIV-1 replication in H9 cell cultures showed that tryptase TL2 is involved in the mechanism of virus internalization into human lymphocytes. The [Leu15, Phe17, Glu52]aprotinin showed a significant retardation of syncytium formation over a period of 5 days in a 1 μM concentration. Similar investigations were performed with recombinant variants of bikunin, the light chain of human inter-α-trypsin inhibitor. Only the single-headed variant [Arg94]82bikunin inhibited slightly the syncytium formation over a period of 2 days in a 2.2 μM concentration. Wild-type bikunin and all full-length variants showed no effect, possibly due to steric hindrance by the second domain of the double-headed inhibitor. 相似文献
995.
Characterization of a redox-active cross-linked complex between cyanobacterial photosystem I and its physiological acceptor flavodoxin. 总被引:2,自引:1,他引:1
下载免费PDF全文
![点击此处可从《The EMBO journal》网站下载免费的PDF全文](/ch/ext_images/free.gif)
A covalent complex between photosystem I and flavodoxin from the cyanobacterium Synechococcus sp. PCC 7002 was generated by chemical cross-linking. Laser flash-absorption spectroscopy indicates that the bound flavodoxin of this complex is stabilized in the semiquinone state and is photoreduced to the quinol form upon light excitation. The kinetics of this photoreduction process, which takes place in approximately 50% of the reaction centres, displays three exponential components with half-lives of 9 microsec, 70 microsec and 1 ms. The fully reduced flavodoxin subsequently recombines with P700+ with a t1/2 of 330 ms. A corresponding flavodoxin semiquinone radical signal is readily observed in the dark by room temperature electron paramagnetic resonance, which reversibly disappears upon illumination. In contrast, the light-induced reduction of oxidized flavodoxin can be observed only by first-flash experiments following excessive dark adaptation. In addition, the docking site of flavodoxin on photosystem I was determined by electron microscopy in combination with image analysis. Flavodoxin binds to the cytoplasmic side of photosystem I at a distance of 7 nm from the centre of the trimer and in close contact to a ridge formed by the subunits PsaC, PsaD and PsaE. 相似文献
996.
Characterization of a redox active cross-linked complex between cyanobacterial photosystem I and soluble ferredoxin. 总被引:1,自引:0,他引:1
下载免费PDF全文
![点击此处可从《The EMBO journal》网站下载免费的PDF全文](/ch/ext_images/free.gif)
A covalent stoichiometric complex between photosystem I (PSI) and ferredoxin from the cyanobacterium Synechocystis sp. PCC 6803 was generated by chemical cross-linking. The photoreduction of ferredoxin, studied by laser flash absorption spectroscopy between 460 and 600 nm, is a fast process in 60% of the covalent complexes, which exhibit spectral and kinetic properties very similar to those observed with the free partners. Two major phases with t(1/2) <1 micros and approximately 10-14 micros are observed at two different pH values (5.8 and 8.0). The remaining complexes do not undergo fast ferredoxin reduction and 20-25% of the complexes are still able to reduce free ferredoxin or flavodoxin efficiently, thus indicating that ferredoxin is not bound properly in this proportion of covalent complexes. The docking site of ferredoxin on PSI was determined by electron microscopy in combination with image analysis. Ferredoxin binds to the cytoplasmic side of PSI, with its mass center 77 angstroms distant from the center of the trimer and in close contact with a ridge formed by the subunits PsaC, PsaD and PsaE. This docking site corresponds to a close proximity between the [2Fe- 2S] center of ferredoxin and the terminal [4Fe-4S] acceptor FII of PSI and is very similar in position to the docking site of flavodoxin, an alternative electron acceptor of PSI. 相似文献
997.
Sandra Turconi Jochen Kruip Gerd Schweitzer Matthias Rögner Alfred R. Holzwarth 《Photosynthesis research》1996,49(3):263-268
Picosecond time-resolved fluorescence measurements have been performed as a function of emission wavelengths in order to investigate the possible functional differences between monomeric and trimeric Photosystem I (PS I) particles from a cyanobacterium Synechocystis. Applying global analysis, four kinetic components were found necessary to describe the fluorescecne decay for both monomers and trimers of PS I. The lifetimes and spectra of the respective components are quite similar, indicating that they can be attributed to identical processes in both the monomers and trimers. It is concluded that both forms of PS I are capable of efficient energy transfer and charge separation, in agreement with a physiological role of both forms. Small differences in the fluorescence decays are discussed in terms of a slightly higher ratio of red emitting pigments per reaction centre in trimers of PS I. A comparison to Synechococcus PS I particles reveals the higher red chlorophyll content of the latter.Abbreviations -DM-
-dodecyl-maltoside
- Chl-
chlorophyll
- CMC-
critical micellar concentration
- DAS-
decay-associated spectrum
- DCM-
4-dicyano-methylene-2-methyl-6-(-dimethyl-aminostyryl)-4h-pyran
- FWHM-
full-width at half-maximum
- P700-
primary electron donor of Photosystem I
- PS-
photosystem
- RC-
reaction centre 相似文献
998.
Cellular Expression and Proteolytic Processing of Presenilin Proteins Is Developmentally Regulated During Neuronal Differentiation 总被引:2,自引:0,他引:2
Anja Capell Rainer Saffrich †Jean-Christophe Olivo ‡Liane Meyn Jochen Walter Jürgen Grünberg §Paul Mathews §Ralph Nixon ‡Carlos Dotti Christian Haass 《Journal of neurochemistry》1997,69(6):2432-2440
Abstract: We have determined the expression of the Alzheimer's disease-associated proteins presenilin-1 and presenilin-2 in primary cultures of rat hippocampal neurons. Neurons highly express presenilin-1 and presenilin-2, whereas both proteins were not detected in astrocytes. Further, we have analyzed the subcellular localization and expression in rat hippocampal neurons during development. Although presenilin proteins were localized predominantly to the endoplasmic reticulum in nonneuronal cells transfected with presenilin cDNAs, in neurons, presenilin proteins were also found in compartments not staining with antibodies to grp78(BiP). Presenilin-1 and presenilin-2 were predominantly detected in vesicular structures within the somatodendritic compartment with much less expression in axons. Polarized distribution of presenilin-1 and presenilin-2 differs slightly, with more presenilin-2 expressed in axons compared with presenilin-1. Presenilin expression was found to be developmentally regulated. Presenilin expression strongly increased during neuronal differentiation until full morphological polarization and then declined. No full-length presenilin-1 or presenilin-2 could be detected within cell lysates. At early developmental stages the expected ~34-kDa N-terminal proteolytic fragment of presenilin-1 and the ~38-kDa fragment of presenilin-2 were detected. Later during differentiation we predominantly detected a ~38-kDa fragment for presenilin-1 and a ~42-kDa fragment for presenilin-2. By epitope mapping, we show that these slower migrating peptides represent N-terminal proteolytic fragments, cleaved C-terminal to the conventional site of processing. It is noteworthy that both presenilin-1 and presenilin-2 undergo alternative proteolytic cleavage at the same stage of neuronal differentiation. Regulation of presenilin expression and proteolytic processing might have implications for the pathological as well as the biological function of presenilins during aging in the human brain. 相似文献
999.
Synaptopodin: An Actin-associated Protein in Telencephalic Dendrites and Renal Podocytes 总被引:31,自引:1,他引:30
下载免费PDF全文
![点击此处可从《The Journal of cell biology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Peter Mundel Hans W. Heid Thomas M. Mundel Meike Krüger Jochen Reiser Wilhelm Kriz 《The Journal of cell biology》1997,139(1):193-204
Transforming growth factor-β (TGFβ) is a dimeric peptide growth factor which regulates cellular differentiation and proliferation during development. Most cells secrete TGFβ as a large latent TGFβ complex containing mature TGFβ, latency associated peptide, and latent TGFβ-binding protein (LTBP)-1. The biological role of LTBP-1 in development remains unclear. Using a polyclonal antiserum specific for LTBP-1 (Ab39) and three-dimensional collagen gel culture assay of embryonic heart, we examined the tissue distribution of LTBP-1 and its functional role during the formation of endocardial cushion tissue in the mouse embryonic heart. Mature TGFβ protein was required at the onset of the endothelial-mesenchymal transformation to initiate endocardial cushion tissue formation. Double antibody staining showed that LTBP-1 colocalized with TGFβ1 as an extracellular fibrillar structure surrounding the endocardial cushion mesenchymal cells. Immunogold electronmicroscopy showed that LTBP-1 localized to 40–100 nm extracellular fibrillar structure and 5–10-nm microfibrils. The anti–LTBP-1 antiserum (Ab39) inhibited the endothelial-mesenchymal transformation in atrio-ventricular endocardial cells cocultured with associated myocardium on a three-dimensional collagen gel lattice. This inhibitory effect was reversed by administration of mature TGFβ proteins in culture. These results suggest that LTBP-1 exists as an extracellular fibrillar structure and plays a role in the storage of TGFβ as a large latent TGFβ complex. 相似文献
1000.
Titus Kuehne B Kelly Gleason Maythem Saeed Daniel Turner Jochen Weil David F Teitel Charles B Higgins Phillip Moore 《Journal of applied physiology》2005,99(4):1422-1427
This study was conducted to determine the effects of chronic combined pulmonary stenosis and pulmonary insufficiency (PSPI) on right (RV) and left ventricular (LV) function in young, growing swine. Six pigs with combined PSPI were studied, and data were compared with previously published data of animals with isolated pulmonary insufficiency and controls. Indexes of systolic function (stroke volume, ejection fraction, and cardiac functional reserve), myocardial contractility (slope of the end-systolic pressure-volume and change in pressure over time-end-diastolic volume relationship), and diastolic compliance were assessed within 2 days of intervention and 3 mo later. Magnetic resonance imaging was used to quantify pulmonary insufficiency and ventricular volumes. The conductance catheter was used to obtain indexes of the cardiac functional reserve, diastolic compliance, and myocardial contractility from pressure-volume relations acquired at rest and under dobutamine infusion. In the PSPI group, the pulmonary regurgitant fraction was 34.3 +/- 5.8%, the pressure gradient across the site of pulmonary stenosis was 20.9 +/- 20 mmHg, and the average RV peak systolic pressure was 70% systemic at 12 wk follow-up. Biventricular resting cardiac outputs and cardiac functional reserves were significantly limited (P < 0.05), LV diastolic compliance significantly decreased (P < 0.05), but RV myocardial contractility significantly enhanced (P < 0.05) compared with control animals at 3-mo follow-up. In the young, developing heart, chronic combined PSPI impairs biventricular systolic pump function and diastolic compliance but preserves RV myocardial contractility. 相似文献