全文获取类型
收费全文 | 6367篇 |
免费 | 628篇 |
国内免费 | 10篇 |
出版年
2022年 | 46篇 |
2021年 | 96篇 |
2020年 | 82篇 |
2019年 | 71篇 |
2018年 | 94篇 |
2017年 | 78篇 |
2016年 | 119篇 |
2015年 | 218篇 |
2014年 | 244篇 |
2013年 | 294篇 |
2012年 | 373篇 |
2011年 | 415篇 |
2010年 | 266篇 |
2009年 | 217篇 |
2008年 | 325篇 |
2007年 | 371篇 |
2006年 | 351篇 |
2005年 | 346篇 |
2004年 | 300篇 |
2003年 | 277篇 |
2002年 | 305篇 |
2001年 | 86篇 |
2000年 | 91篇 |
1999年 | 105篇 |
1998年 | 93篇 |
1997年 | 65篇 |
1996年 | 51篇 |
1995年 | 59篇 |
1994年 | 50篇 |
1993年 | 50篇 |
1992年 | 59篇 |
1991年 | 63篇 |
1990年 | 62篇 |
1989年 | 53篇 |
1988年 | 49篇 |
1987年 | 41篇 |
1986年 | 35篇 |
1985年 | 47篇 |
1984年 | 34篇 |
1983年 | 45篇 |
1982年 | 47篇 |
1981年 | 53篇 |
1980年 | 53篇 |
1979年 | 41篇 |
1978年 | 32篇 |
1976年 | 43篇 |
1975年 | 37篇 |
1974年 | 27篇 |
1973年 | 27篇 |
1969年 | 24篇 |
排序方式: 共有7005条查询结果,搜索用时 15 毫秒
111.
T. M. Hennessey L. E. Frego J. T. Francis 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》1994,175(5):655-665
Paramecium is a valuable eukaryotic model system for studying chemosensory transduction, adaptation and cellular sensory integration. While millimolar amounts of many attractants hyperpolarize and cause faster forward swimming, oxidants are repellents that depolarize and cause backward swimming at micromolar concentrations. The non-permeant oxidants cytochrome c, nitro blue tetrazolium and ferricyanide are repellents with half maximal concentrations of 0.4 M, 2.2 M and 100 M respectively. In vivo reductase activities follow the same order of potencies. The concentration dependence of the cytochrome c reductase activity is well correlated with cytochrome c-induced depolarizations. This suggests that plasma membrane reduction of external cytochrome c is electrogenic, causing membrane depolarization and chemorepulsion. The reductase activity also appears to be voltage dependent. Depolarization by either K+, Na+, Ca+ or Mg+ correlates with inhibition of both in vivo reductase activities and cytochrome c-induced membrane potential changes. These responses were also seen in deciliated cells, showing that the body plasma membrane is sufficient for the response. Both chloroquine and diphenyleneiodonium inhibited reductase activities but only at unusually high concentrations. This activity showed no pH dependence in the physiological range. We propose that a plasma membrane bound NADPH-dependent reductase controls oxidant-induced depolarizations and consequent chemorepulsion.Abbreviations
bmv
Body plasma membrane vesicles
-
BPS
Bathophenanthroline disulfonate
-
cAMP
Cyclic adenosine monophosphate
-
cmv
Ciliary membrane vesicles
-
cyt c
Cytochrome c
-
DPI
Diphenyleneiodonium
-
EC
50
Concentration for 50% effectiveness
-
FeCN
Ferricyanide [Fe(CN)6–3]
-
FeEDTA
Ethylenediaminetetracetic acid (ferric-sodium salt)
-
GTP
Guanosine 5-triphosphate
-
KCN
Potassium cyanide
-
mM
Millimolar
-
MOPS
3-(N-morpholino) propanesulfonic acid
-
mV
Millivolts
-
NADH
Nicotinamide adenine dinucleotide (reduced form)
-
NADPH
Nicotinamide adenine dinucleotide phosphate (reduced form)
-
NBT
Nitro blue tetrazolium
-
nm
Nanometer
-
pCMB
p-Chloromercuribenzoate
-
PMA
Phorbol 12-myristate 13-acetate
-
s.d.
Standard deviation
-
SOD
Superoxide dismutase
-
Tris
Tris(hydroxymethyl)aminomethane
-
M
Micromolar 相似文献
112.
The human glucagon receptor encoding gene: structure, cDNA sequence and chromosomal localization 总被引:2,自引:0,他引:2
Si Lok Joseph L. Kuijper Laura J. Jelinek Janet M. Kramer Theodore E. Whitmore Cindy A. Sprecher Shannon Mathewes Francis J. Grant Shaula H. Biggs Gary B. Rosenberg Paul O. Sheppard Patrick J. O''Hara Donald C. Foster Wayne Kindsvogel 《Gene》1994,140(2):203-209
Characterization of the human glucagon-receptor-encoding gene (GGR) should provide a greater understanding of blood glucose regulation and may reveal a genetic basis for the pathogenesis of diabetes. A cDNA encoding a complete functional human glucagon receptor (GGR) was isolated from a liver cDNA library by a combination of polymerase chain reaction and colony hybridization. The cDNA encodes a receptor protein with 80% identity to rat GGR that binds [125I] glucagon and transduces a signal leading to increases in the concentration of intracellular cyclic adenosine 3′,5′-monophosphate. Southern blot analysis of human DNA reveals a hybridization pattern consistent with a single GGR locus. In situ hybridization to metaphase chromosome preparations maps the GGR locus to chromosome 17q25. Analysis of the genomic sequence shows that the coding region spans over 5.5 kb and is interrupted by 12 introns. 相似文献
113.
Martin M. Lee Francis H.Y. Green W.Michael Schoel Samuel Schürch 《生物化学与生物物理学报:疾病的分子基础》1994,1226(2):151-162
Cell-substrate adhesion was quantified for two cultured mesothelioma cell lines (epitheliomatus and sarcomatous) on glass, fibronectin and laminin substrates. Interference reflection microscopy (IRM) was used to image the adhesion patterns of cells and a grey level analysis was employed to quantify adhesion. Sarcomatous cells demonstrated marked adhesion to glass and fibronectin-coated substrates but not to laminin-coated substrate, with the greatest adhesion occurring on the fibronectin-coated surface. This adhesion was accompanied by cytoplasmic spreading. By contrast, epitheliomatous cells showed little tendency to adhere to any of the substrates and only showed significant spreading when in contact with the laminin substrate (P < 0.01). A bioassay was used to determine the metastatic potential of each of the cell lines. Via the intravenous route, the sarcomatous cells killed the host rats in 24.7 ± 1.5 (S.D.) days compared to 27.3 ± 0.9 (S.D.) days for the epitheliomatous cells (P < 0.01). After subcutaneous inoculation of tumour cells, the sarcomatous cells killed the host rats in 54.7 ± 0.7 (S.D.) days compared to 48.5 ± 0.5 (S.D.) days for the epitheliomatous cells (P < 0.01). We conclude that the results of the metastasis bioassays were consistent with the predicted behavior of these cell lines based on their ability to adhere to substrates in the in vitro adhesion assays. 相似文献
114.
Cobalt determinations in biological fluids are of great interest in biological or toxicological research programs. Cobalturia
is often chosen as an indicator for a biological monitoring program in occupational exposure to cobalt dusts. The method described
here derives from the IUPAC reference method for nickel determination. It enables cobaltemia and cobalturia to be measured
in small samples (1 mL). The mean usual values for cobalt in biological fluids are very low (2.7 nmol L−1 for serum and 6.7 nmol L−1 for urine), and therefore, thus require an analytical procedure with preconcentration and extraction. The sample is mineralized
by wet acid digestion. After digestion, inorganic cobalt is extracted in form of ammonium pyrrolidine dithiocarbamate complex
into isobutyl methyl ketone and measured in the organic layer by electrothermal atomic absorption spectrometry.
The analytical parameters are described in detail. The extraction output is about 99%. The detection limits are 1.93 and 1.89
nmol L−1 for serum and urine, respectively. Sensitivity (expressed as the concentration that gives a 0.044 absorbance) is 3.4 nmol
L−1 for serum and 3.3 nmol L−1 for urine.
Within-run precision ranged between 3.9 and 2.5% (coefficients of variation) for serum and 4.2 and 1.1% for urine, at 87 and
136 nmol L−1 levels, respectively. Between-run precision ranged between 4.3 and 3.3% (coefficients of variation) for serum and 4.2 and
2.3% for urine, at 87 and 136 nmol L−1 levels, respectively. At very low concentration, 5.7 nmol L−1 for serum and 2.5 nmol L−1 for urine, the between-run precision is, respectively, 19.5 and 28%.
Linearity is effective between 0 and 272 nmol L−1. Interferences and matrix effects are negligible for urine, serum, or plasma samples without hemoglobin. The method is easily
applicable for routine determinations. 相似文献
115.
ACTH peptide fragments demonstrate potent neurotrophic effects on peripheral nerves in situ, central neurons in culture, and have been implicated to have effects on central neurons in vivo. Neurotoxic lesioning of the nigrostriatal system, which depletes the striatum of dopamine, provides a feasible model of central regeneration in which to test these peptides. Male Sprague-Dawley rats were lesioned unilaterally with 6-hydroxydopamine (8 μg/4 μl), infused into the substantia nigra. They were subsequently treated with 10 μg/kg IP of Org 2766 [ACTH/MSH(4–9) analogue] or saline every 24 h starting immediately after the infusion and were observed for 2 weeks. Rotational behavior data indicate that Org 2766 significantly decreases ipsiversive turning (p < 0.05), induced by amphetamine (2 mg/kg), as well as accelerating the onset of denervation supersensitivity induced by apomorphine (0.05 mg/kg). Evaluation of dopamine immunohistochemistry, using an anti-tyrosine hydroxylase antibody, demonstrates an enhanced intensity of staining in the ORG 2766-treated tissue compared to its saline counterpart. This difference is confirmed and quantified through specific high-affinity dopamine uptake. Dopamine uptake is about 17% higher in the striata of animals treated with Org 2766. Higher dopamine uptake levels in these ACTH-treated animals correlate with greater fiber density in this group. Therefore, it appears that treatment with the ACTH/MSH(4–9) analogue Org 2766 (10 μg/kg/24 h) offers a protective effect from 6-OHDA lesions in the substantia nigra as well as accelerating various compensatory mechanisms involved in functional recovery. 相似文献
116.
Jeffrey S. Chamberlain Michael Boehnke Thomas S. Frank Sam Kiousis Junxhe Xu Sun-Wei Guo Elizabeth R. Hauser Robert A. Norum Elizabeth A. Helmbold Dorene S. Markel Sima M. Keshavarzi C. Eugene Jackson Kathleen Calzone Judy Garber Francis S. Collins Barbara L. Weber 《American journal of human genetics》1993,52(4):792-798
Previous studies have demonstrated linkage between early-onset breast cancer and ovarian cancer and genetic markers on chromosome 17q21. These markers define the location of a gene (BRCA1) which appears to be inherited as an autosomal dominant susceptibility allele. We analyzed five families with multiple affected individuals for evidence of linkage to the BRCA1 region. Two of the five families appear to be linked to BRCA1. One apparently linked family contains critical recombinants, suggesting that the gene is proximal to the marker D17S579 (Mfd188). These findings are consistent with the maximum-likelihood position estimated by the Breast Cancer Linkage Consortium and with recombination events detected in other linked families. Linkage analysis was greatly aided by PCR-based analysis of paraffin-embedded normal breast tissue from deceased family members, demonstrating the feasibility and importance of this approach. One of the two families with evidence of linkage between breast cancer and genetic markers flanking BRCA1 represents the first such family of African-American descent to be reported in detail. 相似文献
117.
The decline of tree diversity on newly isolated tropical islands: A test of a null hypothesis and some implications 总被引:9,自引:0,他引:9
Egbert Giles Leigh Jr S. Joseph Wright Edward Allen Herre Francis E. Putz 《Evolutionary ecology》1993,7(1):76-102
Summary Six islands, each less than a hectare in area, were isolated in about 1913 from the mainland of central Panamá by the rising waters of Gatun Lake. By 1980, the diversity of trees on all but one of these islands was far lower than on mainland plots of comparable size. A restricted subset of tree species has spread on these islands, notablyProtium panamense, Scheelea zonensis, Oenocarpus panamanus andSwartzia simplex. We constructed a null model to predict how chance would change tree diversity and the similarity of tree species compositions of different islands, assuming that each mature tree has equal chances of dying and/or reproducing, regardless of its species. This model cannot account for the diminished diversity of the changes in vegetation on these islands: some factors must be favoring a particular set of tree species.Two factors, exposure to wind and absence of mammals, seem needed to bring about the vegetation changes observed on these small islands. Their vegetation shows many signs of wind damage and of adaptation to resist wind, reflecting its exposure to dry season winds and storm winds sweeping across the lake from the west. Their most common tree species appear to have spread because mammals rarely visit these small and isolated islands. Seed of these common species are normally much eaten by mammals and do not need burial by mammals to escape insect attack.A thorough grasp of plant—animal interactions is needed to understand the events that have taken place on these islands. Identifying those keystone animals essential for maintaining plant diversity is a necessary element of reserve design and forest management in the tropics.The US government has the right to retain a non-exclusive, royalty-free license in and to any copyright covering this paper. 相似文献
118.
Two novel microsatellite markers for prenatal prediction of spinal muscular atrophy (SMA) 总被引:1,自引:0,他引:1
K. E. Morrison R. J. Daniels G. K. Suthers G. A. Flynn M. J. Francis P. K. Grewal C. Dennis V. Buckle J. Ignatius V. Dubowitz K. E. Davies 《Human genetics》1993,92(2):133-138
Autosomal recessive spinal muscular atrophy (SMA) has been mapped to a 6-cM interval on chromosome 5q12–13.3, flanked proximally by locus D5S6 and distally by locus D5S112. In this study we describe the isolation of two new microsatellite markers (EF1/2a and EF13/14) near locus D5S125, which lies 2 cM distal to D5S6. We show by linkage analysis and the study of the recombinants in 55 SMA pedigrees that the disease lies in the 4-cM interval between EF1/2a and D5S112. Fluorescence in situ analysis of cosmids from D5S6, EF1/2a and D5S112 confirms the genetic order and relative distance of markers. The microsatellites EF1/2a and EF13/14 are the first highly polymorphic PCR based proximal markers in SMA to be described, and will be of value in prental prediction of the disorder. 相似文献
119.
OBJECTIVES--To identify those important characteristics of doctors'' and patients'' behaviour that distinguish between "good" and "bad" consultations when viewed on videotape; to use these characteristics to develop a reliable instrument for assessing general practitioners'' performance in their own consultations. DESIGN--Questionnaires completed by patients, general practitioner trainers, and general practitioner trainees. Reliability of draft instrument tested by general practitioner trainers. SETTING--All vocational training schemes for general practice in the Northern region of England. SUBJECTS--First stage: 76 patients in seven groups, 108 general practice trainers in 12 groups, and 122 general practice trainees in 10 groups. Second stage: 85 general practice trainers in 12 groups. MAIN OUTCOME MEASURES--Trainers'' ratings of importance; alpha coefficients of draft instrument by trainee, group, and consultation. RESULTS--6890 characteristics of good and bad consultations were consolidated into a draft assessment instrument consisting of 46 pairs of definitions separated by six point bipolar scales. Nine statement pairs given low importance ratings by trainers were eliminated, reducing the instrument to 37 statement pairs. To test reliability, general practitioner trainers used the instrument to assess three consultations. With the exception of one group of trainers, all alpha coefficients exceeded the acceptable level of 0.80. CONCLUSION--The instrument produced is reliable for assessing general practitioners'' performance in their own consultations. 相似文献
120.
David L. Musso Nariman B. Mehta Francis E. Soroko Robert M. Ferris Elizabeth B. Hollingsworth Bernard T. Kenney 《Chirality》1993,5(7):495-500
The synthesis of the enantiomers of bupropion, (rac)-2-tert-butylamino-3′-chloropropiophenone 1 (Wellbutrin®) is described. The enantiomers were compared with the racemate in both the tetrabenazine-induced sedation model and the inhibition of uptake of biogenic amine assay. No significant differences were found in their potencies to reverse tetrabenazine-induced sedation in mice or in their IC50 values as inhibitors of biogenic amine uptake into nerve endings obtained from mouse brain. © 1993 Wiley-Liss, Inc. 相似文献