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排序方式: 共有426条查询结果,搜索用时 15 毫秒
1.
T. Ariga Y. Sakiyama K. Tomizawa S. Imajoh-Ohmi S. Kanegasaki S. Matsumoto 《European journal of pediatrics》1993,152(6):469-472
Molecular genetic analysis was performed in a patient with cytochrome b positive X-linked chronic granulomatous disease. A previous Southern blot study, using a cytochrome b heavy chain cDNA as probe, revealed a Pst I restriction fragment pattern for the cytochrome b heavy chain gene (CYBB) different to that of normal individuals. Since restriction length polymorphism with Pst I has never been observed in control individuals and no abnormal restriction fragment patterns in the patient's CYBB was detected with seven other enzymes used, we focussed on the single Pst I site in the CYBB cDNA as being the only mutation site responsible for his disease. A fragment of the patient's cDNA which included the Pst I site was amplified by reverse polymerase chain reaction, and loss of the Pst I site in the fragment was confirmed by incubation with Pst I. Subsequent sequence analysis of the fragment revealed a point mutation in the Pst I site (cytosine to adenine), substituting glutamic acid for alanine at position 57. 相似文献
2.
白细胞介素—2新的功能位点及其中枢镇痛作用 总被引:2,自引:0,他引:2
白细胞介素-2(IL-2)不仅是重要的免疫调节因子,而且还具有重要的中枢调节作用。本实验以钾离子透入引起大鼠甩尾反应为指标,发现侧脑室注射IL—2能显著提高动物痛阈,并能被纳洛酮所阻断,表示IL-2的中枢镇痛作用可能与阿片受体有关。利用基因定位突变技术获得的无免疫活性IL-2实查体仍具有中枢镇痛作用,表明IL—2分子上发挥镇痛和免疫调节作用的功能位点是相互独立的。纳洛酮能够阻断IL—2的中枢镇痛作用,而不能影响IL—2增殖CTLL-2细胞的作用,提示IL-2发挥镇痛和免疫调节作用可能通过不同的受体途径。IL-2分子中第45位Tyr残基突变为Val后,虽仍保留了免疫活性,但丧失了镇痛功能,表示45位Tyr残基是IL—2发挥中枢镇痛功能的关键残基之一。我们推测IL—2的镇痛功能位点可能在IL—2分子中第45位Tyr残基附近区域。 相似文献
3.
We have studied the lateral rectus muscles and neuromuscular junctions (NMJs) of abducens motoneurons in wobbler (wr/wr) mutant mice from 26 to 58 days of age. The muscles of wr/wr weighed about 70% of the weight of littermate controls and were composed of fiber types comparable to those of controls, as assayed by succinate dehydrogenase activity. The most obvious difference between wr/wr and control NMJs was a reduction in the length of the postjunctional membrane of wr/wr mice. The mutant muscle endplate membrane was only about 70% (6.58 micron) the length of control muscle regions (9.44 micron). There were no obvious differences at the light microscopic level in the distribution of acetylcholine (ACh) receptors at junctional regions or staining of acetylcholinesterase, as assayed with alpha-bungarotoxin binding or enzyme histochemistry. Indirect immunocytochemical studies using antibodies directed against the subunits of the ACh receptor failed to indicate an abnormal presence of immature receptors clustered at the NMJs of wr/wr mice. Our findings suggest that the formation or maintenance of normal postjunctional folds and the differentiation of receptors at the junctions are under independent control during development. Furthermore, the wobbler mutation may affect muscle cell differentiation as well as neuronal differentiation. This mutant mouse should prove a useful model for study of postjunctional fold formation and function. 相似文献
4.
M. H. de Vries F. A. M. Redegeld A. Sj. Koster J. Noordhoek J. G. de Haan R. P. J. Oude Elferink P. L. M. Jansen 《Naunyn-Schmiedeberg's archives of pharmacology》1989,340(5):588-592
Summary Recently, a mutant rat strain was described with a genetic defect for the biliary excretion of organic anions (TR– rats). To determine the possible heterogeneity of the transport systems in liver, intestine and kidney we investigated the transport of the anion 1-naphthol--d-glucuronide (1-NG) in isolated vascularly perfused organ preparations of the rat liver, intestine and kidney of both Wistar rats and TR– rats. 1-NG was administered as such (liver and kidney experiments) or formed intracellularly from 1-naphthol (1-N) (liver and gut experiments). Independent of the type of exposure to 1-NG, the biliary excretion was considerably impaired in TR– rats. In the intestine the total appearance and the vascular/luminal distribution pattern of 1-NG were not significantly different from the values in control rats. Furthermore, no significant disturbance was found with respect to the renal clearance of 1-NG in the TR– rat when compared with the Wistar rat. Thus, the genetic defect in the TR– rat is restricted to an impaired hepatobiliary excretion of 1-NG and does not affect the excretory systems of the intestine and kidney. These results suggest that the excretion of 1-NG by the liver, intestine and kidney involves distinct organ-specific transport systems. 相似文献
5.
Ulrike Fuhrmann Karsten Parczyk Michael Klotzbücher Helmut Klocker A. C. B. Cato 《Journal of molecular medicine (Berlin, Germany)》1998,76(7):512-524
Antihormones are by definition antagonists of steroid hormone action. They interact with the ligand binding domains of steroid
hormone receptors and competitively inhibit the action of the receptors by mechanisms that are not quite understood. In certain
cases antihormones also exhibit agonistic activity especially in connection with certain naturally occurring receptor mutants.
These observations together with findings of indiscriminate interaction of antihormones with several classes of steroid receptors
have necessitated a search of more effective and reliable antihormones. Recent advances in the resolution of the crystal structure
of the ligand binding domains of certain members of the steroid receptor family and identification of non-liganded activation
of steroid receptors have produced considerable information that can be harnessed into a fruitful search for a new generation
of antihormones.
Received: 19 June 1997 / Accepted: 10 October 1997 相似文献
6.
cag致病岛缺失的中国幽门螺杆菌突变菌株的构建及鉴定 总被引:1,自引:0,他引:1
7.
目的:体外构建野生型人白细胞介素-13(whIL-13)及变异型人白细胞介素-13(mhIL-13)与增强型绿色荧光蛋白(EGFP)融和蛋白真核表达载体,分析其在COS-7细胞中的表达和亚细胞定位。方法:以RT-PCR方法扩增whIL-13、mhIL-13全长编码基因,构建EGFP-whIL-13、EGFP-mhIL-13融和蛋白真核表达载体,转染COS-7细胞,以激光扫描共聚焦显微镜观察融合蛋白的表达及其在细胞内的分布情况。结果:两种融和蛋白表达载体均构建正确,将其转染COS-7细胞后,在阳性克隆胞浆内均可见明亮的绿色荧光,胞核空虚。结论:成功构建EGFP-whIL-13、EGFP-mhIL-13融和蛋白表达载体,并在COS-7细胞中得到表达,表达的两种融和蛋白细胞内分布特征没有区别,均位于胞浆内。 相似文献
8.
C. Strazielle R. Lalonde L. Riopel M.I. Botez T.A. Reader 《Journal of chemical neuroanatomy》1996,10(2):157-171
The neurological cerebellar mutant lurcher is characterized by a primary degeneration of Purkinje cells as well as a retrograde secondary partial degeneration of cerebellar granule cells and inferior olivary neurons. Since serotonin (5-HT) has been implicated in the modulation of excitatory amino acid systems of the cerebellum, the 5-HT innervation of the normal and lurcher mice was examined by quantifying uptake sites using [3H]citalopram autoradiography, and by biochemical assays of the indoles 5-HT, 5-hydroxy-
-tryptophan and 5-hydroxyindole-3-acetic acid using high-performance liquid chromatography. Comparable results were found between [3H]citalopram binding and 5-HT tissue concentrations in different brain regions. The highest [3H]citalopram labelling was observed in defined structures of the mesencephalic and upper pontine regions, in limbic structures, in hypothalamus and in discrete thalamic divisions, while the lowest labelling of uptake sites was documented in cerebellum and brainstem reticular formation. In lurcher mutants, the histology confirmed cell degeneration and the reduction in width, leading to 65%, 45% and 25% atrophies of total cerebellum, deep nuclei and inferior olivary nucleus, respectively. The [3H]citalopram labelling corrected for surface loss was 45% and 20% higher in cerebellar deep nuclei and red nucleus, respectively, but remained unchanged in the cerebellar cortex and inferior olivary nucleus. Moreover, higher labelling was found in nucleus raphe dorsalis, ventral tegmental area, inferior colliculus, locus coeruleus, pontine central grey and anterior thalamic nuclei, areas known to be part of cerebellar afferent and efferent systems. The present results indicate that in such pathological conditions as described for the lurcher mutant, the 5-HT system may modulate motor function not only at the level of the cerebellum, but also in other forebrain structures functionally related to the motor system. 相似文献
9.
10.
O. Popanda G. Fox H. W. Thielmann 《Journal of molecular medicine (Berlin, Germany)》1995,73(5):259-268
To investigate whether DNA replication in malignant cells deviates from that of normal cells we compared DNA polymerases , , and from normal rat liver to the enzymes from fast-growing (malignant) Novikoff hepatoma cells. DNA polymerases were purified 300-fold by three chromatographic steps. Characterization included measurement of physicochemical constants (including sedimentation coefficients, diffusion coefficients, calculation of relative molecular masses), quantitation of catalytic activities using specific DNA primer templates (K
m values) and inhibitors (K
i values), and identification of polypeptides which are strongly associated with DNA polymerases. Comparison of physicochemical and catalytic properties of DNA polymerases from both sources revealed similarities but also some important differences. DNA primase associated with DNA polymerase , and 3–5 exonuclease accompanying DNA polymerases and had similar activities. In contrast, the DNA-binding domain of DNA polymerases and from hepatoma cells was altered since K
m values, determined with the specific primer templates gapped calf thymus DNA and poly(dA·dT), were higher. Furthermore, sedimentation and diffusion coefficients, Stokes' radii, and frictional coefficient ratios of DNA polymerases and from malignant cells significantly deviated. In addition, when the dNTP-binding sites were probed with specific inhibitors (aphidicolin, butylphenyl-dGTP, carbonyldiphosphonate, and dideoxy-TTP), significantly lower K
i values were obtained for the polymerases from Novikoff cells indicating lower affinity of the dNTP binding site to deoxyribonucleoside 5-triphosphates. Altered catalytic and molecular properties are possibly a consequence of malignant transformation. It is to be expected that similar changes occur in DNA polymerases of other tumors. In particular, diminished affinity to primer templates and weakened nucleotide binding leads to lowered specificity of nucleotide selection in the base-pairing process and is therefore likely to cause an enhanced mutation rate during malignant progression.Abbreviations
PCNA 3
Proliferating-cell nuclear antigen
This paper is dedicated to Prof. Dr. R. Neidlein on the occasion of his 65th birthday. 相似文献