全文获取类型
收费全文 | 3607篇 |
免费 | 306篇 |
国内免费 | 5篇 |
专业分类
3918篇 |
出版年
2024年 | 4篇 |
2023年 | 20篇 |
2022年 | 60篇 |
2021年 | 97篇 |
2020年 | 48篇 |
2019年 | 67篇 |
2018年 | 88篇 |
2017年 | 70篇 |
2016年 | 134篇 |
2015年 | 191篇 |
2014年 | 214篇 |
2013年 | 277篇 |
2012年 | 295篇 |
2011年 | 287篇 |
2010年 | 183篇 |
2009年 | 158篇 |
2008年 | 193篇 |
2007年 | 203篇 |
2006年 | 195篇 |
2005年 | 203篇 |
2004年 | 193篇 |
2003年 | 175篇 |
2002年 | 162篇 |
2001年 | 35篇 |
2000年 | 20篇 |
1999年 | 29篇 |
1998年 | 51篇 |
1997年 | 33篇 |
1996年 | 21篇 |
1995年 | 23篇 |
1994年 | 15篇 |
1993年 | 19篇 |
1992年 | 13篇 |
1991年 | 10篇 |
1990年 | 9篇 |
1989年 | 9篇 |
1988年 | 9篇 |
1987年 | 12篇 |
1986年 | 5篇 |
1985年 | 11篇 |
1984年 | 10篇 |
1983年 | 6篇 |
1982年 | 4篇 |
1981年 | 4篇 |
1980年 | 11篇 |
1979年 | 7篇 |
1977年 | 5篇 |
1974年 | 4篇 |
1972年 | 4篇 |
1962年 | 3篇 |
排序方式: 共有3918条查询结果,搜索用时 0 毫秒
1.
2.
The selective serotonin reuptake inhibitor (SSRI) fluoxetine (FLU, Prozac®) is commonly prescribed for depression in pregnant women. This results in SSRI exposure of the developing fetus. However, there are knowledge gaps regarding the impact of SSRI exposure during development. Given the role of serotonin in brain development and its cross-talk with sex hormone function, we investigated effects of developmental exposure to pharmacologically relevant concentrations of FLU (3 and 30 nM (measured)) on brain neurotransmitter levels, gonadal differentiation, aromatase activity in brain and gonads, and the thyroid system, using the Xenopus tropicalis model. Tadpoles were chronically exposed (8 weeks) until metamorphosis. At metamorphosis brains were cryosectioned and levels of serotonin, dopamine, norepinephrine, and their metabolites 5-hydroxyindoleacetic acid, 3,4-dihydroxyphenylacetic acid, and homovanillic acid were measured in discrete regions (telencephalon, hypothalamus and the reticular formation) of the cryosections using high-performance liquid chromatography. Exposure to 30 nM FLU increased the concentration of 5-hydroxyindoleacetic acid in hypothalamus compared with controls. FLU exposure did not affect survival, time to metamorphosis, thyroid histology, gonadal sex differentiation, or aromatase activity implying that the effect on the serotonergic neurotransmitter system in the hypothalamus region was specific. The FLU concentration that impacted the serotonin system is lower than the concentration measured in umbilical cord serum, suggesting that the serotonin system of the developing brain is highly sensitive to in utero exposure to FLU. To our knowledge this is the first study showing effects of developmental FLU exposure on brain neurochemistry. Given that SSRIs are present in the aquatic environment the current results warrant further investigation into the neurobehavioral effects of SSRIs in aquatic wildlife. 相似文献
3.
Robert A. Mueller Thomas J. McCown Ricky D. Hunt Cecilia Lundberg George R. Breese 《Cellular and molecular neurobiology》1990,10(3):327-336
1. | Rats which survived hypoglycemia by insulin, hypoxia by 10% O2, or ischemia by carotid ligation and hypotension to 40 mm Hg, evidenced no changes in cerebrospinal fluid (CSF) uridine. Animals which died soon after the above interventions or as a result of KCl-induced cardiac arrest had elevated CSF uridine concentrations. |
2. | Injection of whole blood or the soluble contents of lysed blood cells into the lateral ventricle of rats reduced CSF uridine to less than one-half normal at 24 hrs but values returned to normal 3 days later. Changes in hypoxanthine resembled those of uridine, but were less dramatic, whereas xanthine concentrations were largely unaltered. Intraventricular injection of plasma or saline did not alter CSF uridine. |
3. | It seems most likely that low CSF uridine concentrations previously reported in head injury patients may be secondary to the effects of blood cell contents in the cerebrospinal fluid, rather than responses to altered metabolism in neurons or glia cells. |
4.
Cecilia Zazueta José A. Holguín Jorge Ramírez 《Journal of bioenergetics and biomembranes》1991,23(6):889-902
We describe a calcium transport that is sensitive to ruthenium red in liposomes reconstituted with mitochondrial extracts. This system is able to build an internally negative membrane potential, which allows the electrogenic influx of Ca2+ and Sr2+. Proteins with molecular weights higher than 35 kDa were incorporated to the vesicles, and enhanced the accumulation of the cation in an energy-dependent fashion. 相似文献
5.
Kenneth H. Astrin Cecilia A. Warner Han-Wook Yoo Paul J. Goodfellow Shih-Feng Tsai Robert J. Desnick 《Human genetics》1991,87(1):18-22
Summary Uroporphyrinogen III synthase [UROS; hydroxymethylbilane hydro-lyase (cyclizing), EC 4.2.1.75] is the fourth enzyme in the human heme biosynthetic pathway. The recent isolation of the cDNA encoding human UROS facilitated its chromosomal localization. Human UROS sequences were specifically amplified by the polymerase chain reaction (PCR) from genomic DNA of two independent panels of human-rodent somatic cell hybrids. There was 100% concordance for the presence of the human UROS PCR product and human chromosome 10. For each of the other chromosomes, there was 19%–53% discordance with human UROS. The chromosomal assignment was confirmed by Southern hybridization analysis of DNA from somatic cell hybrids with the full-length UROS cDNA. Using human-rodent hybrids containing different portions of human chromosome 10, we assigned the UROS gene to the region 10q25.2 q26.3. 相似文献
6.
Enhanced reactive lysis of paroxysmal nocturnal hemoglobinuria erythrocytes by C5b-9 does not involve increased C7 binding or cell-bound C3b 总被引:8,自引:0,他引:8
S I Rosenfeld D E Jenkins J P Leddy 《Journal of immunology (Baltimore, Md. : 1950)》1985,134(1):506-511
The most complement (C)-sensitive type of erythrocytes (E) occurring in paroxysmal nocturnal hemoglobinuria (type III PNH E) have previously been found to exhibit approximately twofold to fourfold greater lysis than normal human E when exposed to isolated human C5b6, C7, C8, and C9 (reactive lysis), in the absence of a known source of C3- or C5-convertases or fluid-phase C3. In further studies on the mechanism of this phenomenon, we now report that C5b6-dependent binding of 125I-C7 to two samples of PNH E (greater than 95% type III) is equal to that found with normal human E at each of several C5b6 inputs tested. Lysis developed by excess C8 and C9, however, was consistently greater for the PNH E. Thus, the exaggerated sensitivity of type III PNH E to reactive lysis cannot be explained by abnormally high uptake of C5b6 or C7 from the fluid phase. Rather, the data indicate that cell-bound C5b67 sites are converted to effective hemolytic sites with greater efficiency on type III PNH E than on normal human E, assuming that the distribution of cell-bound C7 throughout both cell populations is similar. In related studies we have addressed the proposal by other investigators that C3b putatively bound to PNH E in vivo might account for their increased sensitivity to reactive lysis in vitro, by analogy to prior observations on C3b-potentiated reactive lysis of sheep E. The latter hypothesis was made more appealing by the recent discovery that type III PNH E lack an integral membrane protein, decay-accelerating factor (DAF), which in normal E accelerates the decay of membrane-bound C3 convertases. Against this hypothesis, however, is our present finding that preincubation of PNH E with four different goat or rabbit polyclonal antibodies to human C3 failed to inhibit the subsequent reactive lysis of these cells. Under these same conditions, the C3b-dependent increment in reactive lysis of sheep EAC4b3b was abrogated by pretreatment with similar dilutions of these anti-C3 antibodies, generally in association with agglutination. Furthermore, sheep EAC4b3b displayed increased 125I-C7 binding in proportion to augmented lysis, in contrast to the findings with PNH E. Therefore, deficiency of DAF in type III PNH E does not adequately explain their supranormal sensitivity to reactive lysis unless DAF can modulate the terminal lytic steps by a mechanism distinct from its effect on C3 convertase decay. Alternatively, type III PNH E could have a more general abnormality in which DAF deficiency is one manifestation and increased sensitivity to reactive lysis is another. 相似文献
7.
Neural control of the expression of a Ca2+-activated K+ channel involved in the induction of myotonic-like characteristics 总被引:2,自引:0,他引:2
Beatriz U. Ramírez Maria Isabel Behrens Cecilia Vergara 《Cellular and molecular neurobiology》1996,16(1):39-49
Summary 1. Expression of the apamin-sensitive K+ channel (SK+) in rat skeletal muscle is neurally regulated. The regulatory effect of the nerve over the expression of some muscle ion
channels has been attributed to the electrical activity triggered by the nerve and/or to a trophic effect of some molecules
transported from the soma to the axonal endings.
2. SK+ channels apparently are involved in myotonic dystrophy (MD), therefore understanding the factors that regulate their expression
may ultimately have important clinical relevance.
3. To establish if axoplasmic transport is involved in this process, we used two experimental approaches in adult rats: (a)
Both sciatic nerves were severed, leaving a short or a long nerve stump attached to the anterior tibialis (AT). (b) Colchicine
or vinblastine (VBL), two axonal transport blockers of different potencies, was applied on one leg to the sciatic nerve. To
determine whether electrical activity affects the expression of SK+ channels, denervated AT were directly stimulated. The corresponding contralateral muscles were used as controls.
4. With these experimental conditions we measured (a) apamin binding to muscle membranes, (b) muscle contractile characteristics,
and (c) electromyographic activity.
5. In the short- and long-nerve stump experiments, 5 days after denervation125I-apamin binding to AT membranes was 2.0 times higher in the short-stump side. This difference disappeared at longer times.
The delayed expression of SK+ channels in the muscle left with a longer nerve stump can be attributed to the extra axoplasm contained in the longer stump,
which maintains a normally repressive signal for a longer period of time. Ten to 15 days after application of axonal transport
blockers we found that the muscle half-relaxation time increased in the drug-treated side and apamin partially reverted the
prolonged relaxation. Myotonic-like discharges specifically blockable by apamin were always present in the drug-treated leg.125I-Apamin binding, which is undetectable in a microsomal preparation from hind leg control muscles, was increased in the drug-treated
preparations. Apamin binding to denervated and stimulated AT muscles was lower than in the contralateral unstimulated muscles
[3.3±1.0 vs 6.8±0.8 (n=4) fmol/mg protein].
6. Our results demonstrate that electrical activity and axoplasmic transport are involved in the control of expression of
SK+ in rat skeletal muscle. However, the increased expression of this channel induces myotonic-like characteristics that are
reversed by apamin. This myotonic activity could be a model for MD. 相似文献
8.
The nervous system of Tricladida. I. Neuroanatomy ofProcerodes littoralis (Maricola,Procerodidae): An immunocytochemical study 总被引:3,自引:0,他引:3
Maria Reuter Margaretha K. S. Gustafsson Cecilia Sahlgren David W. Halton Aaron G. Maule Chris Shaw 《Invertebrate neuroscience : IN》1995,1(2):113-122
The organization of the nervous system ofProcerodes littoralis (Tricladida, Maricola, Procerodidae) was studied by immunocytochemistry, using antibodies to authentic flatworm neuropeptide
F (NPF) (Moniezia expansa). Compared to earlier investigations of the neuroanatomy of tricladid flatworms, the pattern of NPF immunoreactivity inProcerodes littoralis reveals differences in the following respects: 1. Shape and structure of the brain. 2. Number and composition of longitudinal
nerve cords. 3. Shape of branches of, and transverse connections between, main ventral nerve cords. 4. Composition of the
pharyngeal nervous system. The rich innervation by NPF immunoreactive (IR) fibres and cells of the subepithelial muscle layer,
the pharynx musculature and the musculature of the male copulatory apparatus indicates a neurotransmitter or neuromodulatory
influence on muscular activity. 相似文献
9.
Cecilia Del Casino Yi-Qin Li Alessandra Moscatelli Monica Scali Antonio Tiezzi Mauro Cresti 《Biology of the cell / under the auspices of the European Cell Biology Organization》1993,79(2):125-132
Summary— The distribution of microtubules was investigated in Nicotiana tabacum pollen tubes at different stages of tube growth by immunofluorescence microscopy. Using specific antibodies, the presence of microtubules consisting of different tubulin isoforms was tested. α-, β- and tyrosinated α-tubulin were present within the tube, whereas the acetylated form was lacking. The presence of tubulin subunits in pollen tube extracts was also investigated by immunoblotting analyses. The use of a confocal laser scanning microscope integrated with computer-assisted imaging, allowed a detailed visualization of the microtubule distribution and organization. Cytoplasmic microtubules organized as short bundles with various orientations were detected at the apex of long tubes. 相似文献