全文获取类型
收费全文 | 15355篇 |
免费 | 1150篇 |
出版年
2023年 | 152篇 |
2022年 | 230篇 |
2021年 | 592篇 |
2020年 | 378篇 |
2019年 | 473篇 |
2018年 | 556篇 |
2017年 | 520篇 |
2016年 | 727篇 |
2015年 | 1069篇 |
2014年 | 1022篇 |
2013年 | 1182篇 |
2012年 | 1361篇 |
2011年 | 1263篇 |
2010年 | 788篇 |
2009年 | 649篇 |
2008年 | 862篇 |
2007年 | 766篇 |
2006年 | 686篇 |
2005年 | 560篇 |
2004年 | 507篇 |
2003年 | 461篇 |
2002年 | 394篇 |
2001年 | 184篇 |
2000年 | 132篇 |
1999年 | 123篇 |
1998年 | 97篇 |
1997年 | 56篇 |
1996年 | 52篇 |
1995年 | 39篇 |
1994年 | 39篇 |
1993年 | 44篇 |
1992年 | 40篇 |
1991年 | 35篇 |
1990年 | 32篇 |
1989年 | 22篇 |
1988年 | 33篇 |
1987年 | 32篇 |
1986年 | 25篇 |
1985年 | 31篇 |
1984年 | 27篇 |
1983年 | 24篇 |
1982年 | 21篇 |
1981年 | 16篇 |
1980年 | 16篇 |
1979年 | 25篇 |
1978年 | 17篇 |
1977年 | 16篇 |
1976年 | 13篇 |
1974年 | 16篇 |
1972年 | 11篇 |
排序方式: 共有10000条查询结果,搜索用时 46 毫秒
991.
† John R. Guyton ‡Sara E. Miller §Margaret E. Martin §Wasiuddin A. Khan §Allen D. Roses §Warren J. Strittmatter 《Journal of neurochemistry》1998,70(3):1235-1240
Abstract: Although the critical role of apolipoprotein E (apoE) allelic variation in Alzheimer's disease and in the outcome of CNS injury is now recognized, the functions of apoE in the CNS remain obscure, particularly with regard to lipid metabolism. We used density gradient ultracentrifugation to identify apoE-containing lipoproteins in human CSF. CSF apoE lipoproteins, previously identified only in the 1.063–1.21 g/ml density range, were also demonstrated in the 1.006–1.060 g/ml density range. Plasma lipoproteins in this density range include low-density lipoprotein and high-density lipoprotein (HDL) subfraction 1 (HDL1 ). The novel CSF apoE lipoproteins are designated HDL1 . No immunoreactive apolipoprotein A-I (apo A-I) or B could be identified in the CSF HDL1 fractions. Large lipoproteins 18.3 ± 6.6 nm in diameter (mean ± SD) in the HDL1 density range were demonstrated by electron microscopy. Following fast protein liquid chromatography of CSF at physiologic ionic strength, apoE was demonstrated in particles of average size greater than particles containing apoA-I. The largest lipoproteins separated by this technique contained apoE without apoA-I. Thus, the presence of large apoE-containing lipoproteins was confirmed without ultracentrifugation. Interconversion between the more abundant smaller apoE-HDL subfractions 2 and 3 and the novel larger apoE-HDL1 is postulated to mediate a role in cholesterol redistribution in brain. 相似文献
992.
Morphogenesis from several explant types excised from in-vitro-grown plantlets of a Brazilian eggplant (Solanum melongena L.) variety (F-100) was evaluated in response to thidiazuron (TDZ). Leaves and cotyledons were found to be the most responsive
explants. Optimal shoot bud induction rates (75–100 buds/explant) were achieved in the presence of 0.2 μm TDZ. Organogenic calli were transferred to growth regulator free MS medium before shoot excision. Rooting was induced on
half-strength MS medium supplemented with 0.6 μm IAA.
Received: 1 March 1997 / Revision received: 29 October 1997 / Accepted: 15 November 1997 相似文献
993.
Sara B.-M. Whittaker Ruth Boetzel Colin MacDonald Lu-Yun Lian Ansgar J. Pommer Ann Reilly Richard James Colin Kleanthous Geoffrey R. Moore 《Journal of biomolecular NMR》1998,12(1):145-159
The cytotoxic activity of the secreted bacterial toxin colicin E9 is due to a non-specific DNase housed in the C-terminus of the protein. Double-resonance and triple-resonance NMR studies of the 134-amino acid15 N- and 13C/15N-labelled DNase domain are presented. Extensive conformational heterogeneity was evident from the presence of far more resonances than expected based on the amino acid sequence of the DNase, and from the appearance of chemical exchange cross-peaks in TOCSY and NOESY spectra. EXSY spectra were recorded to confirm that slow chemical exchange was occurring. Unambiguous sequence-specific resonance assignments are presented for one region of the protein, Pro65-Asn72, which exists in two slowly exchanging conformers based on the identification of chemical exchange cross-peaks in 3D 1H-1H-15N EXSY-HSQC, NOESY-HSQC and TOCSY-HSQC spectra, together with C and C chemical shifts measured in triple-resonance spectra and sequential NH NOEs. The rates of conformational exchange for backbone amide resonances in this stretch of amino acids, and for the indole NH of either Trp22 or Trp58, were determined from the intensity variation of the appropriate diagonal and chemical exchange cross-peaks recorded in 3D1 H-1H-15N NOESY-HSQC spectra. The data fitted a model in which this region of the DNase has two conformers, NA and NB, which interchange at 15 °C with a forward rate constant of 1.61 ± 0.5 s-1 and a backward rate constant of 1.05 ± 0.5 s-1. Demonstration of this conformational equilibrium has led to a reappraisal of a previously proposed kinetic scheme describing the interaction of E9 DNase with immunity proteins [Wallis et al. (1995) Biochemistry, 34, 13743–13750 and 13751–13759]. The revised scheme is consistent with the specific inhibitor protein for the E9 DNase, Im9, associating with both the NA and NB conformers of the DNase and with binding only to the NB conformer detected because the rate of dissociation of the complex of Im9 and the NA conformer, NAI, is extremely rapid. In this model stoichiometric amounts of Im9 convert, the E9 DNase is converted wholly into the NBI form. The possibility that cis–trans isomerisation of peptide bonds preceding proline residues is the cause of the conformational heterogeneity is discussed. E9 DNase contains 10 prolines, with two bracketing the stretch of amino acids that have allowed the NA NB interconversion to be identified, Pro65 and Pro73. The model assumes that one or both of these can exist in either the cis or trans form with strong Im9 binding possible to only one form. 相似文献
994.
995.
V. L. M. Pádua L. D. Fernandes D. E. de Oliveira E. Mansur 《In vitro cellular & developmental biology. Plant》1998,34(4):285-288
An efficient clonal propagation procedure for a Brazilianindica rice subspecies was developed with shoot apex explants. Shoot apices were excised from 4-d-old seedlings and cultured on
MS medium supplemented with 8.9 μM 6-benzyladenine. The efficiency of shoot production was influenced by growth regulators and light treatments to the donor
plant. Explants derived from seedlings growth in the presence of 10.7 μM naphthaleneacetic acid and in the absence of light showed significantly increased regeneration capacity as compared to control
explants. Anatomical analysis of the new shoot meristems revealed that they originated from preexisting apical and axillary
meristem as well as from the mesocotyl parenchyma. 相似文献
996.
Ackee toxicity is associated with consumption of the fruit of the tree Blighia sapida. The problem is endemic in Jamaica, and a number of cases have been reported in the U.S. among Jamaican immigrants. Illness is associated with the method of preparation of the fruit and its ripeness. Malnourished individuals and children appear to be the most susceptible. Levels of the toxic compound, hypoglycin, which are found in the arils and seeds of the fruit, significantly decrease in the arils with ripeness (from 1000 ppm to <0.1?ppm). Symptoms of ackee poisoning in humans occur 6 to 48 hours after ingestion and include vomiting, muscular and mental exhaustion, hypoglycemia, coma and death. Intravenous glucose relieves the hypoglycemia. The most likely mechanism of action occurs through the incorporation of hypoglycin into fatty acid metabolic pathways. Hypoglycin or its primary metabolite methylenecyclopropyl-acetyl-CoA inhibits the oxidation of fatty acids and leucine and the activity of acyl-CoA dehydrogenases. The dose required to elicit acute responses is not known with any precision, nor is it possible to eliminate the likelihood of adverse effects with long-term ingestion of the toxin. Ingestion of unripe aril or pod and seeds represents a significant health hazard; this hazard diminishes considerably with the consumption of properly processed or prepared ripe fruit. 相似文献
997.
Effect of simulated microgravity on vascular contractility 总被引:9,自引:0,他引:9
Purdy R. E.; Duckles S. P.; Krause D. N.; Rubera K. M.; Sara D. 《Journal of applied physiology》1998,85(4):1307-1315
Microgravity was simulated inSprague-Dawley (SD) and Wistar (W) rats by using a tail harness toelevate the hindquarters, producing hindlimb unweighting (HU). After 20 days of HU treatment, blood vessels from both HU and control rats werecut into 3-mm rings and mounted in tissue baths for the measurement ofisometric contraction. HU treatment decreased the contractile responseto 68 mM K+ in abdominal aortafrom W rats. HU treatment also decreased the contraction to 68 mMK+ in carotid arteries from bothrat strains and in femoral arteries from W but not SD rats. HUtreatment reduced the maximal response to norepinephrine in allarteries except the femoral from SD rats. HU treatment reduced themaximal response of jugular vein from W rats to 68 mMK+ but had no effect on thatresponse in femoral vein from either rat strain. HU treatment also hadno significant effect on the maximal response to norepinephrine inveins. These results demonstrate that HU treatment caused a nearlyuniversal reduction of contractility in arteries, but generally had noeffect in veins. 相似文献
998.
Sara Dodd Graham A. Place R. L. Hall Stephen E. Harding 《European biophysics journal : EBJ》1998,28(1):38-47
We have used two different approaches to determine hydrodynamic parameters for mucins secreted by guinea-pig tracheal epithelial
cells in primary culture. Cells were cultured under conditions that promote mucous cell differentiation. Secreted mucins were
isolated as the excluded fraction from a Sepharose CL-4B gel filtration column run under strongly dissociating conditions.
Biochemical analysis confirmed the identity of the high molecular weight material as mucins. Analytical ultracentrifugation
was used to study the physical properties of the purified mucins. The weight average molecular mass (M
w
) for three different preparations ranged from 3.3×106 to 4.7×106 g/mol (corresponding to an average structure of 1 – 2 subunits), and the sedimentation coefficient from 25.5 to 35 S. Diffusion
coefficients ranging from 4.5×10–8 to 6.4×10–8 cm2/s were calculated using the Svedberg equation. A polydispersity index (M
z
/M
w
) of ∼1.4 was obtained. Diffusivity values were also determined by image analysis of mucin granule exocytosis captured by
videomicroscopy. The time course of hydration and dissolution of mucin was measured and a relationship is presented which
models both phases, each with first order kinetics, in terms of a maximum radius and rate constants for hydration and dissolution.
A median diffusivity value of 8.05×10–8 cm2/s (inter-quartile range = 1.11×10–7 to 6.08×10–8 cm2/sec) was determined for the hydration phase. For the dissolution phase, a median diffusivity value of 6.98×10–9 cm2/s (inter-quartile range = 1.47×10–8 to 3.25×10–9 cm2/sec) was determined. These values were compared with the macromolecular diffusion coefficients (D
20,w
) obtained by analytical ultracentrifugation. When differences in temperature and viscosity were taken into account, the resulting
D
37,g
was within the range of diffusivity values for dissolution. Our findings show that the physicochemical properties of mucins
secreted by cultured guinea-pig tracheal epithelial cells are similar to those of mucins of the single or double subunit type
purified from respiratory mucus or sputum. These data also suggest that measurement of the diffusivity of dissolution may
be a useful means to estimate the diffusion coefficient of mucins in mucus gel at the time of exocytosis from a secretory
cell.
Received: 10 March 1998 / Accepted: 27 March 1998 相似文献
999.
Luciana Di Ciero Maria L. V. Oliva Ricardo Torquato Peter Köhler Jürgen K. P. Weder José Camillo Novello Claudio A. M. Sampaio Benedito Oliveira Sergio Marangoni 《Journal of Protein Chemistry》1998,17(8):827-834
Trypsin inhibitors of two varieties of Bauhinia variegata seeds have been isolated and characterized. Bauhinia variegata candida trypsin inhibitor (BvcTI) and B. variegata lilac trypsin inhibitor (BvlTI) are proteins with M
r
of about 20,000 without free sulfhydryl groups. Amino acid analysis shows a high content of aspartic acid, glutamic acid, serine, and glycine, and a low content of histidine, tyrosine, methionine, and lysine in both inhibitors. Isoelectric focusing for both varieties detected three isoforms (pI 4.85, 5.00, and 5.15), which were resolved by HPLC procedure. The trypsin inhibitors show K
i
values of 6.9 and 1.2 nM for BvcTI and BvlTI, respectively. The N-terminal sequences of the three trypsin inhibitor isoforms from both varieties of Bauhinia variegata and the complete amino acid sequence of B. variegata var. candida L. trypsin inhibitor isoform 3 (BvcTI-3) are presented. The sequences have been determined by automated Edman degradation of the reduced and carboxymethylated proteins of the peptides resulting from Staphylococcus aureus protease and trypsin digestion. BvcTI-3 is composed of 167 residues and has a calculated molecular mass of 18,529. Homology studies with other trypsin inhibitors show that BvcTI-3 belongs to the Kunitz family. The putative active site encompasses Arg (63)–Ile (64). 相似文献
1000.
Shubha Priyamvada Sara A. Khan Md.Wasim Khan Sheeba Khan Neelam Farooq Farah Khan A.N.K. Yusufi 《Prostaglandins, leukotrienes, and essential fatty acids》2010,82(1):35-44
Human and animal exposure demonstrates that uranium is nephrotoxic. However, attempts to reduce it were not found suitable for clinical use. Dietary fish oil (FO) enriched in ω-3 fatty acids reduces the severity of cardiovascular and renal diseases. Present study investigates the protective effect of FO on uranyl nitrate (UN)-induced renal damage. Rats prefed with experimental diets for 15 days, given single nephrotoxic dose of UN (0.5 mg/kg body weight) intraperitoneally. After 5 d of UN treatment, serum/urine parameters, enzymes of carbohydrate metabolism, brush border membrane (BBM), oxidative stress and phosphate transport were analyzed in rat kidney. UN nephrotoxicity was characterized by increased serum creatinine and blood urea nitrogen. UN increased the activity of lactate dehydrogenase and NADP-malic enzyme whereas decreased malate, isocitrate and glucose-6-phophate dehydrogenases; glucose-6-phophatase, fructose-1, 6-bisphosphatase and BBM enzyme activities. UN caused oxidant/antioxidant imbalances as reflected by increased lipid peroxidation, activities of superoxide dismutase, glutathione peroxidase and decreased catalase activity. Feeding FO alone increased activities of enzymes of glucose metabolism, BBM, oxidative stress and Pi transport. UN-elicited alterations were prevented by FO feeding. However, corn oil had no such effects and was not similarly effective. In conclusion, FO appears to protect against UN-induced nephrotoxicity by improving energy metabolism and antioxidant defense mechanism. 相似文献