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1.
F Leonessa V Boulay A Wright E W Thompson N Brünner R Clarke 《Acta oncologica (Stockholm, Sweden)》1992,31(2):115-123
Many breast tumors appear to follow a predictable clinical pattern, being initially responsive to endocrine therapy and to cytotoxic chemotherapy but ultimately exhibiting a phenotype resistant to both modalities. Using the MCF-7 human breast cancer cell line as an example of an 'early' phenotype (estrogen and progesterone receptor positive, steroid responsive, low metastatic potential), we have isolated and characterized a series of hormone-independent but hormone-responsive variants (MIII and MCF7/LCC1). However, these variants remain responsive to both antiestrogens and cytotoxic drugs (methotrexate and colchicine). MIII and MCF7/LCC1 cells appear to mimic some of the critical aspects of the early progression to a more aggressive phenotype. An examination of the phenotype of these cells suggests that some hormone-independent breast cancer cells are derived from hormone-dependent parental cells. The development of a hormone-independent phenotype can arise independently of acquisition of a cytotoxic drug resistant phenotype. 相似文献
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Nadia Sdiqui Khalil Arar Patrick Midoux Roger Mayer Michel Monsigny Annie-Claude Roche 《Drug delivery》1995,2(1):63-72
The Ha-ras oncogene promotes cell proliferation. Antisense oligonucleotides complementary to the ras gene sequence encompassing a mutated codon 12 selectively induce a cell proliferation inhibition. However, the concentration required to reach an effective inhibition is high due to the low efficiency of the oligonucleotide crossing through cell membranes, leading to a low concentration in the cytosol and/or the nucleoplasm. In the present paper, we show that anti-ras oligonucleotides linked to a glycosylated carrier, serum albumin bearing mannose 6-phosphate residues, are more efficient than free oligonucleotides or oligonucleotides bound to an unglycosylated carrier at inhibiting proliferation of a human tumor mammary cell line expressing the mutated Ha-ras. Using fluorescein-labeled neoglycoproteins and fluorescein-labeled oligonucleotides bound to neoglycoproteins, flow cytometry and confocal microscopy revealed that (i) these tumor cells express a membrane lectin specific for mannose 6-phosphate-bearing proteins, (ii) the membrane lectin actively mediates the uptake of macromolecules substituted with mannose 6-phosphate, and (iii) the fluorescein-labeled oligonucleotides bound to the neoglycoprotein accumulate in intracellular vesicles. Furthermore, with antisense oligonucleotides carried by the neoglycoproteins, the concentration required to inhibit cell proliferation is lower than that of the carrier-free antisense oligonucleotides. 相似文献
4.
Lower airway inflammatory responses to repeated very-low-dose allergen challenge in allergic rhinitis and asthma 总被引:2,自引:0,他引:2
BACKGROUND: Low-dose allergen challenge (LDAC) may be a useful tool for studying the capacity of allergens to induce airway inflammation in atopic subjects. OBJECTIVE: To evaluate lower airway inflammatory changes following repeated inhalation of very low doses of allergen (VLDAC) in non-asthmatic subjects with allergic rhinitis (NAAR) compared with mild allergic asthmatic subjects (AA). METHODS: Fourteen NAAR and 11 AA were seen out of the pollen season and had skin prick tests with common aeroallergens. Baseline spirometry (S) and methacholine challenge (MC) were done and blood and induced sputum (IS) differential cell counts were obtained. Each subject underwent VLDAC on four consecutive mornings with a relevant allergen. S, MC, and blood and IS samplings were repeated 6 h after the second and fourth VLDAC and one week later. RESULTS: Although there were, as expected, no changes in FEV1 or PC20 in either group, mean percentage eosinophils on IS were significantly increased in NAAR on day 2 of VLDAC and decreased in all but one subject on day 4, with a tendency to return to baseline levels one week later. In AA, there was a non-significant trend for sputum eosinophils to increase on day 2; four subjects showed a decrease of eosinophils on day 4 of VLDAC. There was a correlation between eosinophil cationic protein (ECP) levels and eosinophil counts in NAAR throughout the study. There were no variations in other sputum cells or blood inflammatory cells. CONCLUSION: VLDAC can increase the percentage of eosinophils in IS of NAAR subjects without associated respiratory symptoms nor physiological modifications. A reduction in eosinophilic response despite repeated exposure, more common in NAAR subjects, suggests an adaptation process that needs to be further evaluated. 相似文献
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Alpha-smooth muscle actin as a marker for soft tissue tumours: a comparison with desmin 总被引:1,自引:0,他引:1
The immunoreactivity of a range of vascular and non-vascular smooth muscle tumours, rhabdomyosarcomas, and non-myoid lesions has been examined with the use of a monoclonal antibody to smooth muscle-specific actin and the muscle intermediate filament, desmin. In all cases of smooth muscle-derived tumours, the alpha-actin antibody yielded superior results. Staining of the myofibroblasts of fibromatoses was also seen. In contrast to desmin, immunoreactivity was not exhibited by rhabdomyosarcomas. We propose that this monoclonal antibody to alpha-smooth muscle actin is a useful addition to the panel of reagents used for the characterization of soft tissue proliferations and tumours. The technical aspects of the application of this monoclonal antibody to immunohistochemistry are discussed. 相似文献
7.
The unavoidable senescence process that limits the vegetative growth of Podospora anserina is always associated with an accumulation of various classes of circular, tandemly arranged, defective mitochondrial DNA
molecules (senDNAs). The monomers of the senDNAs belonging to the so-called β class share a common core, but differ in both their length and termini. To understand the mechanism leading to their formation,
we have determined the junction sequence of 36 senDNA β monomers present in various senescent cultures. In most cases, we observe that: (1) short direct repeats precisely bound
the senDNA β termini and (2) one copy of the repeats is retained in the senDNA sequence. Moreover, PCR analysis of the mitochondrial DNA
of some of the senescent cultures, has allowed us to detect another genome which is exactly lacking the sequence of the senDNA
β found in the culture. These results demonstrate that an intramolecular unequal cross-over occurring between short direct
repeats can generate deleted mtDNA molecules in P. anserina. In addition, the polymorphism displayed by one pair of repeats allows us to establish that this cross-over may be associated
with a short conversion tract spanning a few (about 15) nucleotides.
Received: 16 May / 11 November 1996 相似文献
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Charlotte V. Hobbs Jan Drobeniuc Theresa Kittle John Williams Paul Byers Panayampalli S. Satheshkumar Kengo Inagaki Meagan Stephenson Sara S. Kim Manish M. Patel Brendan Flannery CDC COVID- Response Team CDC COVID- Response Team Bailey Alston Shanna J. Bolcen Darbi Boulay Peter Browning Li Cronin Ebenezer David Tonya Hayden Han Li Travis Lim Panagiotis Maniatis Palak Patel Mathew Pauly Amanda Poe Lili Punkova Vera Semenova Evelene P. Steward-Clark Alexandra Tejada Briana Zellner 《MMWR. Morbidity and mortality weekly report》2021,70(9):312
10.
Dopamine D2 receptor knock-out mice are insensitive to the hypolocomotor and hypothermic effects of dopamine D2/D3 receptor agonists. 总被引:5,自引:0,他引:5
The dopamine (DA) D2-like family of receptors is comprised of three subtypes, the D2, D3, and D4 receptors. It has been suggested that the potency of DA receptor agonists to produce hypothermia and hypolocomotion in rodents correlates more strongly with the in vitro affinity for, or potency (mitogenesis test) at the D3 than at the D2 subtype. However, it has recently been reported that when tested in DA D3 receptor knock-out mice, several DA D2/D3 receptor agonists (7-OH-DPAT, PD 128907 and quinelorane) induced levels of hypothermia and decreases of locomotor activity similar to those obtained in control (wild-type) mice. These results do not argue in favour of an implication of DA D3 receptors in these in vivo effects. In order to investigate whether the DA D2 receptor is the subtype that mediates hypothermia and hypolocomotion produced by DA D2/D3 receptor agonists, we tested the effects of ip administration of the DA D2/D3 receptor agonists 7-OH-DPAT and PD 128907, on core temperature and locomotor activity in DA D2 receptor knock-out mice (homozygotes: D2(-/-) and heterozygotes: D2(+/-)), and in wild-type (D2(+/+)) mice. 7-OH-DPAT (0.1-3 mg/kg) and PD 128907 (1-10 mg/kg) induced hypothermia and decreased locomotion in D2(+/+) mice, but had no effects in D2(-/-) mice; the magnitude of the hypothermic and locomotor-reducing effects of these two agonists in D2(+/+) mutants was approximately half that of D2(+/+) mice. During the first 10 min in the activity chambers, the level of spontaneous locomotor activity of D2(-/-) individuals was almost 50% below that of D2(+/+) mice; basal locomotor activity of D2(+/-) mice was between that of D2(-/-) and D2(+/+) individuals. Neither type of mutant showed spontaneous catalepsy or deficits in forelimb muscle strength (grip-strength test). These results show that the presence of DA D2 receptors is necessary for the expression of the locomotor- and core temperature-decreasing effects of DA D2/D3 receptor agonists such as 7-OH-DPAT and PD 128907. 相似文献