全文获取类型
收费全文 | 1116篇 |
免费 | 131篇 |
专业分类
1247篇 |
出版年
2022年 | 7篇 |
2021年 | 10篇 |
2018年 | 11篇 |
2016年 | 15篇 |
2015年 | 30篇 |
2014年 | 38篇 |
2013年 | 48篇 |
2012年 | 67篇 |
2011年 | 99篇 |
2010年 | 30篇 |
2009年 | 43篇 |
2008年 | 43篇 |
2007年 | 41篇 |
2006年 | 37篇 |
2005年 | 35篇 |
2004年 | 45篇 |
2003年 | 23篇 |
2002年 | 25篇 |
2001年 | 31篇 |
2000年 | 29篇 |
1999年 | 21篇 |
1998年 | 7篇 |
1997年 | 11篇 |
1996年 | 9篇 |
1995年 | 11篇 |
1994年 | 7篇 |
1993年 | 9篇 |
1992年 | 30篇 |
1991年 | 15篇 |
1990年 | 20篇 |
1989年 | 20篇 |
1988年 | 20篇 |
1987年 | 18篇 |
1986年 | 24篇 |
1985年 | 28篇 |
1984年 | 14篇 |
1983年 | 19篇 |
1982年 | 18篇 |
1981年 | 8篇 |
1980年 | 21篇 |
1979年 | 28篇 |
1978年 | 14篇 |
1977年 | 14篇 |
1974年 | 14篇 |
1973年 | 17篇 |
1972年 | 11篇 |
1971年 | 9篇 |
1970年 | 10篇 |
1969年 | 10篇 |
1968年 | 10篇 |
排序方式: 共有1247条查询结果,搜索用时 15 毫秒
21.
D Haynes P Hall D Clark 《Virchows Archiv. B, Cell pathology including molecular pathology》1983,42(3):289-301
Liver and heart from a substrain of the NZR/Gd rat in which there is an inherited deficiency of liver phosphorylase b kinase was examined by light and electron microscopy and compared to material from a related, but normal substrain. Hepatic tissue differed markedly from that of control animals. Hepatocytes contained more than twice as much free glycogen and visible lipid. Glycogen particles had an abnormal appearance and some glycogen was sequestered within large, membrane-bound vesicles. Hepatocyte lysosomes were increased by a third and mean cell volume by more than half. Lobular architecture was distorted by the presence of enlarged, irregularly-shaped hepatocytes. Free glycogen was present in the space of Disse and sinusoids and within lysosomes in Kupffer cells. There were increased amounts of collagen in the space of Disse. The changes resemble those described in human glycogen storage disease IXa. A study of hepatic tissue from fasted rats showed that affected animals have an impaired ability to mobilise their liver glycogen stores. An increase in visible lipid also occurred in affected, fasted animals. Cardiac tissue appeared to be normal. 相似文献
22.
Genetic and biochemical consequences of thymidylate stress 总被引:8,自引:0,他引:8
We have examined the genetic and biochemical consequences of thymidylate stress in haploid and diploid strains of the simple eukaryote Saccharomyces cerevisiae (Bakers' yeast). Previously we reported that inhibition of dTMP biosynthesis causes "thymineless death" and is highly recombinagenic, but apparently not mutagenic, at the nuclear level; however, it is mutagenic for mitochondria. Concurrent provision of dTMP abolishes these effects. Conversely, excess dTMP is highly mutagenic for nuclear genes. It is likely that DNA strand breaks are responsible for the recombinagenic effects of thymidylate deprivation; such breaks could be produced by reiterative uracil incorporation and excision in DNA repair patches. In our experiments, thymidylate stress was produced both by starving dTMP auxotrophs for the required nucleotide and also by blocking de novo synthesis of thymidylate by various antimetabolites. We found that the antifolate methotrexate is a potent inducer of mitotic recombination (both gene conversion and mitotic crossing-over). This suggests that the gene amplification associated with methotrexate resistance in mammalian cells could arise, in part, by unequal sister-chromatid exchange induced by thymidylate stress. In addition, several sulfa drugs, which impede de novo folate biosynthesis, also have considerable recombinagenic activity. 相似文献
23.
D G Reid K Gajjar S P Robinson D M Hickey G M Benson C Haynes P D Leeson C M Whittaker 《Chemistry and physics of lipids》1991,60(2):143-151
In an investigation of novel potential bile acid sequestrants, the affinities of the sodium salts of the glycine and taurine conjugates of naturally occurring bile acids (cholate, deoxycholate, chenodeoxycholate and lithocholate) for several cationic ammonium bile acid derivatives have been investigated by measurements of the extent to which the derivatives are able to precipitate the bile acids. This is roughly proportional to the lipophilicity of the interacting species. Thus, amino and ammonium derivatives of cholic acid do not precipitate taurocholate or glycocholate to any great extent, whereas ammonium derivatives of deoxycholate and lithocholate are much more effective. To complement the precipitation measurements, high resolution 13C-NMR has been applied to investigate the weaker interactions between the ammonium cholate derivative and glycocholate, glycodeoxycholate and glycochenodeoxycholate. Addition of either of the latter two bile acids to the cationic ammonium compound results in considerable broadening of the 13C resonances of both species, indicating the formation of relatively rigid structures. In addition, we have used T2 relaxation enhancement induced by spin-labelled fatty acids to examine the mechanism of interaction with bile acids of amphiphilic anions, which might compete with bile acids for sites on bile acid sequestrants. Low concentrations of 16-DOXY L-Stearate dramatically broaden the 13C-NMR resonances of deoxycholate carbons 19, 18 and 7 in particular, while 5-DOXY L-Stearate exerts much less specific effects. These results have been incorporated into a snapshot model of bile acid-fatty acid interactions. 相似文献
24.
Vincent C. K. Chiu Donald Mouring Brant D. Watson Duncan H. Haynes 《The Journal of membrane biology》1980,56(2):121-132
Summary The binding of the anionic fluorescent probe 1-anilino-8-naphthalene-sulfonate (ANS–) was used to estimate the surface potential of fragmented sarcoplasmic reticulum (SR) derived from rabbit skeletal muscle. The method is based on the observation that ANS– is an obligatory anion whose equilibrium constant for binding membranes is proportional to the electrostatic function of membrane surface potential, exp(e0/kT, where 0 is the membrane surface potential,e is the electronic charge, andkT has its usual meaning. The potential measured is characteristic of the ANS– bindings of phosphatidylcholine head groups and is about one-third as large as the average surface potential predicted by the Gouy-Chapman theory. At physiological ionic strength the surface potentials, measured by ANS–, referred to as the aqueous phase bathing the surface, were in the range –10 to –15 mV. This was observed for the outside and inside surfaces of the Ca2+-ATPase-rich fraction of theSR and for both surfaces of theSR fraction rich in acidic Ca2+ binding proteins. The inside and outside surfaces were differentiated on the basis of ANS– binding kinetics observed in stopped-flow rapid mixing experiments. A mechanism by which changes in Ca2+ concentration could give rise to an electrostatic potential across the membrane and possibly result in changes in Ca2+ permeability.The dependence of the surface potential on the monovalent ion concentration in the medium was used together with the Gouy-Chapman theory to determine the lower limits for the surface charge density for the inside and outside surfaces of the two types ofSR. Values for the Ca2+-ATPase richSR fraction were between 2.9×103 and 3.8×103 esu/cm2, (0.96×10–6 and 1.26×10–6 C/cm2) with no appreciable transmembrane asymmetry. A small amount of asymmetry was observed in the values for the inside and outside surfaces of the fraction rich in acidic binding proteins which were ca. 6.6×103 and ca. 2.2×103 esu/cm2 (2.2×10–6 and 0.73×10–6 C/cm). The values could be accounted for by the known composition of negatively-charged phospholipids in theSR. The acidic Ca2+ binding proteins were shown to make at most a small contribution to the surface charge, indicating that their charge must be located at least several tens of Å from the membrane surface. The experiments gave evidence for a Donnan effect on the K+ distribution in the fraction rich in acidic binding proteins. This could be accounted for by the known concentration of acidic binding proteins in thisSR fraction.The equilibrium constant for ANS– was shown to be more sensitive to changes in the divalent cation concentration than to changes in the monovalent cation concentration, as predicted by the Gouy-Chapman theory. Use of these findings together with the stopped-flow rapid mixing techniques constitutes a method for rapid and continuous monitoring of changes in ion concentrations in theSR lumen. 相似文献
25.
26.
Divalent cations induce the aggregation of chromaffin granule ghosts (CG membranes) at millimolar concentrations. Monovalent cations produce the same effect at 100-fold higher concentrations. The kinetics of the dimerization phase were followed by light-scattering changes observed in stopped-flow rapid mixing experiments. The rate constant for Ca2+-induced dimerization (kapp) is 0.86-1.0 x 10(9) M-1sec-1, based on the "molar" vesicle concentration. This value is close to the values predicted by theory for the case of diffusion-controlled reaction (7.02 x 10(9) M-1sec-1), indicating that there is no energy barrier to dimerization. Arrhenius plots between 10 degrees and 42 degrees C support this; the activation energy observed, +4.4 Kcal, is close to the value (4.6-4.8 Kcal) predicted for diffusion control according to theory. Artificial vesicles prepared from CG lipids were also found to have cation-induced aggregation, but the rates (values of kapp) were less than 1/100 as large as those with native CG membranes. Also, significant differences were found with respect to cation specificity. It is concluded that the slow rates are due to the low probability that the segments of membrane which approach will be matched in polar head group composition and disposition. Thus large numbers of approaches are necessary before matched segments come into aposition. The salient features of the chromaffin granule membrane aggregation mechanism are as follows: (a) In the absence of cations capable of shielding and binding, the membranes are held apart by electrostatic repulsion of their negatively charged surfaces. (b) The divalent and monovalent cation effects on aggregation are due to their ability to shield these charges, allowing a closer approach of the membrane surfaces. (c) The major determinants of the aggregation rates of CG membranes are proteins which protrude from the (phospholipid) surface of the membrane and serve as points of primary contact. Transmembrane contact between these proteins does not require full neutralization of the surface charge and surface potential arising from the negatively charged phospholipids. (d) After contact between proteins is established, the interaction between membranes can be strengthened through transmembrane hydrogen bonding of phosphatidyl ethanolamine polar head groups, divalent cation-mediated salt bridging, and segregation of phosphatidylcholine out of the region of contact. 相似文献
27.
28.
Stephen N. Haynes 《Applied psychophysiology and biofeedback》1976,1(1):121-126
In this case report, a 25-year-old female with chronic dysphagia spastica(difficulty swallowing because of constriction of the throat muscles) was treated with 20 sessions of frontal electromyographic(EMG) biofeedback and home-relaxation practice. The subject monitored on a 10-point scale her difficulty swallowing during meals for 2 months prior to treatment, during treatment, and after treatment. There was a significant decrease in reported difficulty swallowing associated with frontalis EMG feedback. Improvement was maintained at a 6-month follow-up. 相似文献
29.
Dickinson ME Murray BA Haynes SM Waters CW Longmuir KJ 《Differentiation; research in biological diversity》2002,70(4-5):172-180
Fluorescent proteins have emerged as an ideal fluorescent marker for studying cell morphologies in vital systems. These proteins were first applied in whole organisms with established germ-line transformation protocols, but now it is possible to label cells with fluorescent proteins in other organisms. Here we present two ways to introduce GFP expressing plasmids into avian embryos for vital confocal and two-photon imaging. First, electroporation is a powerful approach to introduce GFP into the developing neural tube, offering several advantages over dye labeling. Second, we introduce a new lipid-based transfection system for introducing plasmid DNA directly to a small group of injected cells within live, whole embryos. These complementary approaches make it possible to transfect a wide-range of cell types in the avian embryo and the bright, stable, uniform expression of GFP offers great advantages for vital fluorescence imaging. 相似文献
30.
Istem Fer Anthony K. Gardella Alexey N. Shiklomanov Eleanor E. Campbell Elizabeth M. Cowdery Martin G. De Kauwe Ankur Desai Matthew J. Duveneck Joshua B. Fisher Katherine D. Haynes Forrest M. Hoffman Miriam R. Johnston Rob Kooper David S. LeBauer Joshua Mantooth William J. Parton Benjamin Poulter Tristan Quaife Ann Raiho Kevin Schaefer Shawn P. Serbin James Simkins Kevin R. Wilcox Toni Viskari Michael C. Dietze 《Global Change Biology》2021,27(1):13-26
In an era of rapid global change, our ability to understand and predict Earth's natural systems is lagging behind our ability to monitor and measure changes in the biosphere. Bottlenecks to informing models with observations have reduced our capacity to fully exploit the growing volume and variety of available data. Here, we take a critical look at the information infrastructure that connects ecosystem modeling and measurement efforts, and propose a roadmap to community cyberinfrastructure development that can reduce the divisions between empirical research and modeling and accelerate the pace of discovery. A new era of data‐model integration requires investment in accessible, scalable, and transparent tools that integrate the expertise of the whole community, including both modelers and empiricists. This roadmap focuses on five key opportunities for community tools: the underlying foundations of community cyberinfrastructure; data ingest; calibration of models to data; model‐data benchmarking; and data assimilation and ecological forecasting. This community‐driven approach is a key to meeting the pressing needs of science and society in the 21st century. 相似文献