全文获取类型
收费全文 | 8616篇 |
免费 | 567篇 |
国内免费 | 1篇 |
出版年
2023年 | 43篇 |
2022年 | 94篇 |
2021年 | 174篇 |
2020年 | 97篇 |
2019年 | 158篇 |
2018年 | 218篇 |
2017年 | 160篇 |
2016年 | 275篇 |
2015年 | 405篇 |
2014年 | 476篇 |
2013年 | 578篇 |
2012年 | 737篇 |
2011年 | 659篇 |
2010年 | 429篇 |
2009年 | 423篇 |
2008年 | 565篇 |
2007年 | 517篇 |
2006年 | 461篇 |
2005年 | 476篇 |
2004年 | 423篇 |
2003年 | 393篇 |
2002年 | 371篇 |
2001年 | 80篇 |
2000年 | 62篇 |
1999年 | 79篇 |
1998年 | 93篇 |
1997年 | 67篇 |
1996年 | 67篇 |
1995年 | 45篇 |
1994年 | 66篇 |
1993年 | 46篇 |
1992年 | 45篇 |
1991年 | 38篇 |
1990年 | 32篇 |
1989年 | 30篇 |
1988年 | 23篇 |
1987年 | 17篇 |
1986年 | 11篇 |
1985年 | 14篇 |
1984年 | 22篇 |
1983年 | 13篇 |
1982年 | 20篇 |
1981年 | 17篇 |
1980年 | 13篇 |
1979年 | 9篇 |
1978年 | 17篇 |
1977年 | 13篇 |
1976年 | 14篇 |
1975年 | 10篇 |
1938年 | 8篇 |
排序方式: 共有9184条查询结果,搜索用时 15 毫秒
81.
S. Aime Mauro Botta S. Geninatti Crich Giovanni B. Giovenzana Roberto Pagliarin Maurizio Piccinini Massimo Sisti Enzo Terreno 《Journal of biological inorganic chemistry》1997,2(4):470-479
A novel heptacoordinating ligand consisting of a thirteen-membered tetraazamacrocycle containing the pyridine ring and bearing
three methylenephosphonate groups (PCTP-[13]) has been synthesized. Its Gd(III) complex displays a remarkably high longitudinal
water proton relaxivity (7.7 mM–1 s–1 at 25 °C, 20 MHz and pH 7.5) which has been accounted for in terms of contributions arising from (1) one water molecule
bound to the metal ion, (2) hydrogen-bonded water molecules in the second coordination sphere, or (3) water molecules diffusing
near the paramagnetic chelate. Variable-temperature 17O-NMR transverse relaxation data indicate that the residence lifetime of the metal-bound water molecule is very short (8.0 ns
at 25 °C) with respect to the Gd(III) complexes currently considered as contrast agents for magnetic resonance imaging. Furthermore,
GdPCTP-[13] interacts with human serum albumin (HSA), likely through electrostatic forces. By comparing water proton relaxivity
data for the GdPCTP-[13]-HSA adduct, measured as a function of temperature and magnetic field strength, with those for the
analogous adduct with GdDOTP (a twelve-membered tetraaza macrocyclic tetramethylenephosphonate complex lacking a metal-bound
water molecule), it has been possible to propose a general picture accounting for the main determinants of the relaxation
enhancement observed when a paramagnetic Gd(III) complex is bound to HSA. Basically, the relaxation enhancement in these systems
arises from (1) water molecules in the hydration shell of the macromolecule and protein exchangeable protons which lie close
to the interaction site of the paramagnetic complex and (2) the metal bound water molecule(s). As far as the latter contribution
is concerned, the interaction with the protein causes an elongation of the residence lifetime of the metal-bound water molecule,
which limits, to some extent, the potential relaxivity enhancement expected upon the binding of the paramagnetic complex to
HSA.
Received: 27 January 1997 / Accepted: 12 May 1997 相似文献
82.
Hydrological cycle and interannual variability of the aquatic community in a temporary saline lake (Fuente de Piedra,Southern Spain) 总被引:4,自引:2,他引:2
García Carlos M. García-Ruiz Roberto Rendón Manuel Niell F. Xavier Lucena Juan 《Hydrobiologia》1997,345(2-3):131-141
Fuente de Piedra is a shallow, temporary saline lake whoseseasonal behavior is strongly dependent on the annual hydrologicalbudget. In this study, we outline the characteristics of Fuente dePiedra Lake for two years that had different hydrological budgets.The high precipitations in 1989–90 caused the lake not to dry asusual, and decreased both salinity and the amplitude of changes.There were also differences in nutrient dynamics, with generallylower concentrations of soluble reactive phosphorus and ammonium,whereas in the more humid year nitrate showed a distinct maximum inwinter. Winter bloom chlorophyll a concentrations were alsomuch higher in 1989–90 (>600 g l-1) but there wasalso a winter productive phase that was presumably poorly coupledwith consumption processes that predominate in spring. Planktonicassemblages were different between years. Highly halotolerantphytoplankton species (Dunaliella salina and D. viridis) became scarcer, and especially two previouslyunrecorded diatoms (Cyclotella sp. and Chaetoceros sp.)became dominant in the bloom time in the wet year. The speciesrichness of the zooplankton increased in the wet year, with newspecies appearing that were not collected during 1987–88(Branchinectella media, Daphnia mediterranea, Macrothrix sp.,Arctodiaptomus salinus, Cyclops sp., Sigara sp...).There was also a much higher development of macrophytes (Ruppiadrepanensis, Althenia orientalis, Lamprothamnium papulosum)and bird populations, especially flamingoes (Phoenicopterusruber).Important interannual variations in this sort of system pointto the need for long term studies to observe the whole range ofstates that define the lake as an entity. 相似文献
83.
Alexander Mironov Antonino Colanzi Maria Giuseppina Silletta Giusy Fiucci Silvio Flati Aurora Fusella Roman Polishchuk Alexander Mironov Jr. Giuseppe Di Tullio Roberto Weigert Vivek Malhotra Daniela Corda Maria Antonietta De Matteis Alberto Luini 《The Journal of cell biology》1997,139(5):1109-1118
We have investigated the role of the ADP- ribosylation induced by brefeldin A (BFA) in the mechanisms controlling the architecture of the Golgi complex. BFA causes the rapid disassembly of this organelle into a network of tubules, prevents the association of coatomer and other proteins to Golgi membranes, and stimulates the ADP-ribosylation of two cytosolic proteins of 38 and 50 kD (GAPDH and BARS-50; De Matteis, M.A., M. DiGirolamo, A. Colanzi, M. Pallas, G. Di Tullio, L.J. McDonald, J. Moss, G. Santini, S. Bannykh, D. Corda, and A. Luini. 1994. Proc. Natl. Acad. Sci. USA. 91:1114–1118; Di Girolamo, M., M.G. Silletta, M.A. De Matteis, A. Braca, A. Colanzi, D. Pawlak, M.M. Rasenick, A. Luini, and D. Corda. 1995. Proc. Natl. Acad. Sci. USA. 92:7065–7069). To study the role of ADP-ribosylation, this reaction was inhibited by depletion of NAD+ (the ADP-ribose donor) or by using selective pharmacological blockers in permeabilized cells. In NAD+-depleted cells and in the presence of dialized cytosol, BFA detached coat proteins from Golgi membranes with normal potency but failed to alter the organelle's structure. Readdition of NAD+ triggered Golgi disassembly by BFA. This effect of NAD+ was mimicked by the use of pre–ADP- ribosylated cytosol. The further addition of extracts enriched in native BARS-50 abolished the ability of ADP-ribosylated cytosol to support the effect of BFA. Pharmacological blockers of the BFA-dependent ADP-ribosylation (Weigert, R., A. Colanzi, A. Mironov, R. Buccione, C. Cericola, M.G. Sciulli, G. Santini, S. Flati, A. Fusella, J. Donaldson, M. DiGirolamo, D. Corda, M.A. De Matteis, and A. Luini. 1997. J. Biol. Chem. 272:14200–14207) prevented Golgi disassembly by BFA in permeabilized cells. These inhibitors became inactive in the presence of pre–ADP-ribosylated cytosol, and their activity was rescued by supplementing the cytosol with a native BARS-50–enriched fraction. These results indicate that ADP-ribosylation plays a role in the Golgi disassembling activity of BFA, and suggest that the ADP-ribosylated substrates are components of the machinery controlling the structure of the Golgi apparatus. 相似文献
84.
Consuelo Díaz de la Guardia Roberto Alonso Francisca Alba Francisco Valle 《Aerobiologia》1995,11(1):47-50
We have carried out a study on the annual and daily pollen concentrations from Gramineae over four consecutive years in the atmosphere of Granada (Spain). Samples of pollen grains were collected by the volumetric method with the aid of a Burkard sporetrap. Gramineae, according both to their high sensitizing capacity and to data from allergologists, are responsible for many pollinoses diagnosed in this area. In this work, daily pollen levels from April to July are monitored and the variations identified are interpreted in relation to meteorological conditions. Results indicated that the highest airborne concentrations of Gramineae pollen were found in May and June, although the beginning and intensity of pollination have been variable during these 4 years. 相似文献
85.
Bernardo Celda Clelia Biamonti Maria Jose Arnau Roberto Tejero Gaetano T. Montelione 《Journal of biomolecular NMR》1995,5(2):161-172
Summary A large portion of the 13C resonance assignments for murine epidermal growth factor (mEGF) at pH 3.1 and 28°C has been determined at natural isotope abundance. Sequence-specific 13C assignments are reported for 100% of the assignable C, 96% of the C, 86% of the aromatic and 70% of the remaining peripheral aliphatic resonances of mEGF. A good correlation was observed between experimental and back-calculated C chemical shifts for regions of regular -sheet structure. These assignments also provide the basis for interpreting 1H–13C heteronuclear NOE (HNOE) values in mEGF at natural isotope abundance. Some of the backbone polypeptide segments with high internal mobility, indicated by these 1H–13C HNOE measurements, correlate with locations of residues involved in the putative mEGF-receptor binding site. Using four families of mEGF structures obtained over the last few years, we demonstrate that standard deviations between experimental and back-calculated C values can be used to monitor the refinement of this protein's structure, particularly for -sheet regions. Improved agreement between calculated and observed values of C is correlated with other measures of structure quality, including lowered values of residual constraint violations and more negative values of conformational energy. These results support the view that experimental conformation-dependent chemical shifts, C, can provide a reliable source of information for monitoring the process of protein structure refinement and are potentially useful restraints for driving the refinement.Abbreviations HSQC
heteronuclear single-quantum coherence spectroscopy
- PFG
pulsed-field gradient
- TOCSY
1H-1H total correlation spectroscopy
- EGF
epidermal growth factor
- mEGF
murine EGF
- hEGF
human EGF
- hTGF
human type- transforming growth factor
- DIPSI
spm-locking pulse sequence
- NOE
nuclear Overhauser effect
- HNOE
heteronuclear Overhauser effect 相似文献
86.
A novel chromatin-forming histone H1 homologue is encoded by a dispensable and growth-regulated gene in Bordetella pertussis 总被引:5,自引:1,他引:4
87.
Parodi Armando J. Blank Edward W. Peterson Jerry Ceriani Roberto 《Molecular and cellular biochemistry》1984,58(1-2):157-163
Summary Membranes isolated from mouse and human milk fat globules were found to contain the enzymes responsible for the synthesis of dolichol monophosphate mannose and dolichol monophosphate glucose as well as those involved in the transference of the glycosyl residues from the two dolichol derivatives to dolichol diphosphate oligosaccharides. The levels of most of the enzymes were comparable to those found in mouse mammary gland microsomes. The presence of enzymes involved in protein glycosylation via dolichol derivatives in the milk fat globule membrane provides evidence in favor of an outward flow of membrane components from the rough endoplasmic reticulum, where these enzymes are active in vivo, towards the cell surface. 相似文献
88.
Cristina Casals Carmen Acebal Jesús Pérez-Gil Roberto Arche 《Molecular and cellular biochemistry》1984,63(1):13-20
Summary Lysolecithin:lysolecithin acyltranferase is an enzyme which in several previous studies has shown a dual behavior catalyzing two types of reaction, transacylation or hydrolysis, with the same substrate. Both activities have shown to be dependent on several environmental conditions and among them, the presence of lipids.The addition of several classes of lipids activated in all the cases the enzyme, decreasing the hydrolysis/transacylation molar ratio. This effect was higher for PC/PE/Chol mixture than for other lipids assayed. Circular dichroism spectra of the enzyme did not show any change with the addition of lipids, concluding that the effect of lipids was not due to any structural change in the protein. The hypothesis has been made of an influence of lipids on the physical state of the substrate as well as, possibly, on the enzyme-substrate interaction.The significance of these effects on the physiological role of lysolecithin:lysolecithin acyltransferase from soluble fraction of rabbit lung is discussed.Abbreviations Chol
cholesterol
- CMC
critical micellar concentration
- DPPC
dipalmitoylphosphatidylcholine
- FA
fatty acid
- H/T
hydrolysis/transacylation molar ratio
- LPC
lysophosphatidylcholine
- PC
phosphatidylcholine
- PE
phosphatidylethanolamine
- TG
triglyceride
- UV
ultraviolet 相似文献
89.
The intracellular concentration of S-adenosylmethionine (SAM) and the specific activity of S-adenosylmethionine synthetase (ATP:l-methionine S-adenosyltransferase, EC 2.5.1.6) were examined in wild-typeMucor racemosus, as well as a morphological mutant termedcoy, under conditions designed to prevent the morphogenesis of yeasts to hyphae. When the mutant was grown in a defined medium supplemented with methionine and induced to shift by exposure to air, there was an increase in intracellular SAM analogous to that previously reported with the wild type. However, when thecoy mutant was grown in the absence of methionine, the intracellular concentration decreased dramatically and the mutant failed to undergo the yeast to hypha transition. An inhibitor of SAM synthetase activity, cycloserine, was used to lower the intracellular concentration of SAM in the wild-type organisms. Under these conditions, wild-typeM. racemosus failed to undergo the transition from yeasts to hyphae when exposed to air. 相似文献
90.
Giancarlo Bianchi Roberto Fiocchi Alessandra Tavani Luciano Manara 《Life sciences》1982,30(22):1875-1883
Single doses of naloxone (0.025 to 0.5 mg/kg) or of one of four quaternary narcotic antagonists (i.e. nalorphine allobromide, nalorphine methobromide, naloxone methobromide or naltrexone methobromide, 1 to 60 mg/kg) were given s.c. to rats before morphine, 5 mg/kg i.v. In the absence of antagonists morphine reduced G.I. transit of a charcoal meal to about 15% of drug-free controls and consistently delayed nociceptive reactions (55°C hot plate) in all animals. Doses of antagonists slightly reducing morphine antinociception (centrally effective = A) and restoring G.I. transit to about 50% of drug-free rats (peripherally effective = B) were estimated. The A:B ratio, indicating peripheral selectivity, was at least 8 for any of the quaternary antagonists given 10 min before morphine, but prolonging this interval may have resulted in a lower figure (i.e. less peripheral selectivity) because of reduced A and increased B. This was definitely so for naltrexone methobromide (A:B, > 60 at 10 min, about 1 at 80 min) and was not apparent for nalorphine methobromide according to available data, which for nalorphine allobromide and to a lesser extent for naloxone methobromide showed only an increase in B at intervals longer than 10 min. Both morphine-induced antinociception and inhibition of G.I. transit were reduced by naloxone at the lower doses tested and were fully prevented at the higher. These findings indicate that, unlike naloxone, the investigated quaternary narcotic antagonists are interesting prototype drugs for selective blockade of opiate receptors outside the CNS, although certain critical aspects, possibly biological N-dealkylation to the corresponding tertiary antagonists, condition peripheral selectivity. 相似文献