全文获取类型
收费全文 | 5807篇 |
免费 | 443篇 |
国内免费 | 2篇 |
出版年
2023年 | 15篇 |
2022年 | 33篇 |
2021年 | 68篇 |
2020年 | 50篇 |
2019年 | 51篇 |
2018年 | 79篇 |
2017年 | 70篇 |
2016年 | 117篇 |
2015年 | 185篇 |
2014年 | 262篇 |
2013年 | 342篇 |
2012年 | 348篇 |
2011年 | 388篇 |
2010年 | 261篇 |
2009年 | 252篇 |
2008年 | 342篇 |
2007年 | 369篇 |
2006年 | 341篇 |
2005年 | 347篇 |
2004年 | 305篇 |
2003年 | 287篇 |
2002年 | 304篇 |
2001年 | 68篇 |
2000年 | 57篇 |
1999年 | 81篇 |
1998年 | 109篇 |
1997年 | 86篇 |
1996年 | 74篇 |
1995年 | 58篇 |
1994年 | 63篇 |
1993年 | 66篇 |
1992年 | 49篇 |
1991年 | 56篇 |
1990年 | 40篇 |
1989年 | 58篇 |
1988年 | 45篇 |
1987年 | 31篇 |
1986年 | 42篇 |
1985年 | 34篇 |
1984年 | 31篇 |
1983年 | 24篇 |
1982年 | 52篇 |
1981年 | 33篇 |
1980年 | 33篇 |
1979年 | 23篇 |
1978年 | 16篇 |
1977年 | 24篇 |
1976年 | 16篇 |
1975年 | 21篇 |
1974年 | 15篇 |
排序方式: 共有6252条查询结果,搜索用时 437 毫秒
931.
The conformational space of methyl 6-O-[(R)- and (S)- 1-carboxyethyl]-α-D-galactopyranoside has been investigated. A grid
search employing energy minimization at each grid point over the three major degrees of freedom, namely φ, ψ and ω, identified
low energy regions. The R-isomer shows five low energy conformers within ca. 1 kcal mol−1 of the global energy minimum. The
S-isomer has two conformers within a few tenths of a kcal mol−1 of the global energy minimum. Langevin dynamics simulations
have been have been performed at 300 K for 30 ns of each isomer. The φ dihedral angle has as its major conformer (g−1) for
the R-isomer whereas it is the (g+) conformer for the S-isomer. For the ψ dihedral angle the (t) conformer has the highest
population for both isomers. The dihedral angle ω has the (g+) conformer most highly populated, both for the R- and S-isomer.
The above five and two conformational states for the R- and S-isomers, respectively, make up 90% in each case of the populated
states during the Langevin dynamics (LD) simulations. Rate constants for the ω dihedral angle have been calculated based on
a number correlation function. Three bond homo- and heteronuclear, i.e. proton and carbon-13, coupling constants have been
calculated from the dynamics trajectories for comparison to experimental values. The heteronuclear coupling constant H2′,C6
has been measured for the S-isomer and found to be 3.3 Hz. The J value calculated from the LD simulations, namely 2.6 Hz,
is in fair agreement with experiment. A comparison to the X-ray structure of the R-isomer shows that the conformation of the
crystalline compound occupies the low energy region most highly populated as a single R-conformer (30%) during the LD simulations.
This revised version was published online in August 2006 with corrections to the Cover Date. 相似文献
932.
Christian-Serge Degoute M.-P. Preckel Christian Dubreuil Vincent Banssillon Roland Duclaux 《European journal of applied physiology and occupational physiology》1997,75(4):326-332
The purpose of this work was to show that regulation of the blood flow to the cochlea by the sympathetic nervous system occurs
in humans at the level of the cochlear microcirculation during increases in blood pressure and that its involvement depends
on the pressure level. Eight anaesthetized patients undergoing tympanoplasty for hearing disease took part in a pharmacological
protocol of stimulation and inhibition of the autonomic nervous system (ANS) to provide variations in systolic blood pressure
(BPS) and cochlear blood flow (CBF). The CBF was measured by laser-Doppler flowmetry. Changes in autonomic nerve activity were
brought about by changes in baroreceptor activity (BR) initiated by the injection of an α adrenergic agent before and after
sympathetic and parasympathetic blockade. The CBF variations (δCBF) were plotted against BPS increases at each stage of the ANS inhibition. The BR diminished significantly after α blockade, after α and β blockade,
and after α and β blockade and atropine, by 50% (P < 0.01), 29% (P < 0.05), and 95% (P < 0.001) respectively. The BPS increased significantly (P < 0.01) by 36 (SD 9)%, 47 (SD 1)%, and 67 (SD 16)% respectively. The CBF response to an increase in BPS exhibited two opposing variations in the patients: CBF decreased significantly in one group, and increased significantly
in the other group. In both groups, δCBF decrease and δCBF increase, respectively, were significant after ANS blockade; even
so the decrease and increase, respectively, levelled off at BPS around 160 mmHg before ANS blockade. For BPS below 160 mmHg, correlations between δCBF and BPS were significant before inhibition and after inhibition of ANS. For BPS above 160 mmHg, BPS and δCBF were not correlated before inhibition of ANS, and were significantly correlated after inhibition of ANS. For BPS below 160 mmHg, CBF response to the BPS increase was the same before and after ANS blockade, i.e. ANS control did not predominate; even so, for BPS above 160 mmHg, the CBF response to BPS increase was different before and after ANS blockade: CBF varied significantly after ANS blockade as it varied for BPS below 160 mmHg, while it remained constant before ANS blockade that elicited ANS control of CBF. In conclusion, sympathetic
nerve regulation via its vasomotor tone at the level of cochlear microcirculation occurred markedly when the blood pressure
was above 160 mmHg; the autonomic nervous system would appear to control the cochlear blood flow against large variations
in blood flow in response to hypertensive phenomena.
Accepted: 7 October 1996 相似文献
933.
H. Thorsten Lumbsch Roland Guderley G. Benno Feige 《Plant Systematics and Evolution》1997,205(3-4):179-184
The ascospore septation in 13 species ofDiploschistes was examined. Microcephalic, macrocephalic, as well as irregular ascospore septation were found. In some species and even specimens of some species, different types of spore septation were detected. The taxonomic significance of the character of ascospore septation sequence is questioned, and the distinction of the ordersGraphidales andOstropales, which was primarily based on this character, is rejected.This paper is dedicated to Prof. DrRolf Santesson (Uppsala) on the occasion of his 80th birthday. 相似文献
934.
The clonal shrub, Mahonia aquifolium, is an aggressive invader of some forests in central Germany. We analysed the importance of seedling recruitment for the
local dynamics of these invasive populations. In contrast to many other clonal plants, repeated seedling recruitment takes
place in M. aquifolium, contributing to the colonization of available space within populations. Thus, sexual reproduction is not only important
for dispersal to new sites but also for the local invasion␣process. In situations with grass competition (Calamagrostis epigejos) the number of successful recruits is reduced, and clonal growth is the predominant mode of reproduction. Since seedling
recruitment results in an increasing number of genets as well as ramets, the investigated populations are still below their
carrying capacities. Seedling densities are higher beneath the canopy of adults than outside adult patches, and increase with
increasing cover of adult ramets. The spatially clumped pattern of seedling emergence results in density-dependent mortality
especially in the most crowded seedling clusters. However, adult neighbourhood imposes a much higher mortality. Therefore,
we expect that the importance of seedling recruitment for the dynamics of local M. aquifolium populations will decline as the invasion process continues.
Received: 15 January 1996 / Accepted: 28 September 1996 相似文献
935.
Neal R. Pellis Thomas J. Goodwin Diana Risin Bradley W. McIntyre Roland P. Pizzini David Cooper Tacey L. Baker Glenn F. Spaulding 《In vitro cellular & developmental biology. Animal》1997,33(5):398-405
Summary Immunity relies on the circulation of lymphocytes through many different tissues including blood vessels, lymphatic channels,
and lymphoid organs. The ability of lymphocytes to traverse the interstitium in both nonlymphoid and lymphoid tissues can
be determined in vitro by assaying their capacity to locomote through Type I collagen. In an attempt to characterize potential causes of microgravity-induced
immunosuppression, we investigated the effects of simulated microgravity on human lymphocyte function in vitro using a specialized rotating-wall vessel culture system developed at the Johnson Space Center. This very low shear culture
system randomizes gravitational vectors and provides an in vitro approximation of microgravity. In the randomized gravity of the rotating-wall vessel culture system, peripheral blood lymphocytes
did not locomote through Type I collagen, whereas static cultures supported normal movement. Although cells remained viable
during the entire culture period, peripheral blood lymphocytes transferred to unit gravity (static culture) after 6 h in the
rotating-wall vessel culture system were slow to recover and locomote into collagen matrix. After 72 h in the rotating-wall
vessel culture system and an additional 72 h in static culture, peripheral blood lymphocytes did not recover their ability
to locomote. Loss of locomotory activity in rotating-wall vessel cultures appears to be related to changes in the activation
state of the lymphocytes and the expression of adhesion molecules. Culture in the rotating-wall vessel system blunted the
ability of peripheral blood lymphocytes to respond to polyclonal activation with phytohemagglutinin. Locomotory response remained
intact when peripheral blood lymphocytes were activated by anti-CD3 antibody and interleukin-2 prior to introduction into
the rotating-wall vessel culture system. Thus, in addition to the systemic stress factors that may affect immunity, isolated
lymphocytes respond to gravitational changes by ceasing locomotion through model interstitium. These in vitro investigations suggest that microgravity induces non-stress-related changes in cell function that may be critical to immunity.
Preliminary analysis of locomotion in true microgravity revealed a substantial inhibition of cellular movement in Type I collagen.
Thus, the rotating-wall vessel culture system provides a model for analyzing the microgravity-induced inhibition of lymphocyte
locomotion and the investigation of the mechanisms related to lymphocyte movement. 相似文献
936.
Cacang Suarna Roger T. Dean Peter T. Southwell-Keeley Douglas E. Moore Roland Stocker 《Free radical research》1997,27(4):397-408
In previous work we demonstrated that up to 30 % of cholesteryl linoleate in homogenates of advanced human plaque samples is present in oxidized forms. Here we show that the material from plaque hexane extracts which co-elutes with cholesteryl hydroxylinoleate on reversed phase HPLC (Anal Biochem 1993;213:79), is composed of several isomers of cholesteryl hydroxy- and cholesteryl oxo-octadecadienoate. Enzymatic hydrolysis and measurement of liberated cholesterol and disappearance of the esters revealed that almost all of the material consisted of unoxidized cholesterol esterified to oxidized derivatives of octadeca-dienoate. Semi-preparative reversed-phase HPLC was used to obtain sufficient quantities of this co-eluting material to undertake normal phase HPLC separation of these components. The nature of such separated and isolated compounds was identified, by co-chromatography with authentic standards, UV spectroscopy and chemical ionization and electron impact mass spectrometry, as cholesteryl hydroxy- and cholesteryl oxo-octadecadienoate. These oxidized fatty acids have been observed previously in plaque, in agreement with our new unambiguous demonstration of their presence as cholesteryl esters. The application of the methods described for the separation of the various forms of oxidized cholesteryl octadecadienoate may aid mechanistic studies of in vitro and in vivo lipoprotein lipid oxidation. 相似文献
937.
Roland Peter 《当今生物学》2004,34(4):220-228
938.
D?rthe M Katschinski Lu Le Susann G Schindler Tim Thomas Anne K Voss Roland H Wenger 《Cellular physiology and biochemistry》2004,14(4-6):351-360
Hypoxia-inducible factor (HIF) alpha subunits are induced under hypoxic conditions, when limited oxygen supply prevents prolyl hydroxylation-dependent binding of the ubiquitin ligase pVHL and subsequent proteasomal degradation. A short normoxic half-life of HIF-alpha and a very rapid hypoxic protein stabilization are crucial to the cellular adaptation to changing oxygen supply. However, the molecular requirements for the unusually rapid mechanisms of protein synthesis, folding and nuclear translocation are not well understood. We and others previously found that the chaperone heat-shock protein 90 (HSP90) can interact with HIF-1alpha in vitro. Here we show that HSP90 also interacts with HIF-2alpha and HIF-3alpha, suggesting a general involvement of HSP90 in HIF-alpha stabilization. The PAS B domain, common to all three alpha subunits, was required for HSP90 interaction. ARNT competed with HSP90 for binding to the PAS B domain since an excess of either component inhibited the activity of the other. HSP90 as well as the heterocomplex members HSP70 and p23, but not HSP40, were detected in immunoprecipitations of endogenous cellular HIF-1alpha. While HSP90 and HSP70 bound to HIF-1alpha predominantly under normoxic conditions, ARNT bound to HIF-1alpha primarily under hypoxic conditions, suggesting that ARNT displaced HSP90 from HIF-1alpha following nuclear translocation. Hypoxic accumulation of HIF-1alpha was delayed in a novel cell model deficient for HSP90beta as well as after treatment of wild-type cells with the HSP90 inhibitor geldanamycin, suggesting that HSP90 activity is involved in the rapid HIF-1alpha protein induction. 相似文献
939.
Roland Wacker Stanka Stoeva Karola Pfüller Uwe Pfüller Wolfgang Voelter 《Journal of peptide science》2004,10(3):138-148
The complete primary structure of the A chain of mistletoe lectin III (ML3A), a type II ribosome-inactivating protein, was determined using proteolytic digests of ML3A, HPLC separation of the peptides, Edman degration and MALDI-MS. Based on our results, ML3A consists of 254 amino acid residues, showing a high homology to the A chain of isolectin ML1 with only 24 amino acid residue exchanges. A striking important structural difference compared with ML1A is the lack of the single N-glycosylation site in ML3A due to an amino acid exchange at position 112 (ML1A: NL112GS ==> ML3A: T112GS). The alignment of ML3A with the A chains of ML1, isoabrins, ricin D, Ricinus communis agglutinin and three lectins, identified from the Korean mistletoe Viscum album ssp. coloratum, demonstrates the rigid conservation of all amino acid residues, responsible for the RNA-N-glycosidase activity as reported for ricin D. In addition, the fully determined primary structure of ML3A will give further information about the biological mechanism of mistletoe lectin therapy. 相似文献
940.
Claudia Ludovici Roland Fr?hlich Karsten Vogtt Bj?rn Mamat Mathias Lübben 《European journal of biochemistry》2002,269(10):2630-2637
We developed the synthesis of the caged oxygen donor (micro-peroxo)(micro-hydroxo)bis[bis(bipyridyl)cobalt(III)] complex (HPBC) as nitrate salt, which has, compared with the perchlorate-form described previously [MacArthur, R., Sucheta, A., Chong, F.F. & Einarsdottir, O. (1995) Proc. Natl Acad. Sci. USA, 92, 8105-8109], greatly enhanced solubility. Now, the quantum efficiency of the photolytical release of dioxygen was determined to be 0.4 per photon at a laser wavelength of 308 nm, which was used to observe biological reactions. The X-ray structure of HPBC has been solved, and the molecular interactions of photochemically generated oxygen with cytochrome oxidase were investigated with optical and FT-IR spectroscopy: it acts as acceptor of electrons transferred from prereduced cytochrome bo(3), the heme-copper oxidase from Escherichia coli. FT-IR spectra revealed typical absorbance difference changes in the carbonyl region of cytochrome bo(3), supported by bandshifts due to solvent isotope exchange and by assignment using site-directed mutants. IR difference spectra of the photooxidation reaction using the caged oxygen compound, and of the photoreduction reaction using the caged electron donor FMN, have inverted shapes. The spectroscopic signals of carboxyl groups are thus equivalent in both reactions: the use of chemically produced oxygen allows the observation of the ongoing molecular changes of cytochrome bo(3) oxidase under quasi-physiological conditions. 相似文献