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1.
Summary— KR31080 (2-butyl-5-methyl-6-(1-oxopyridin-2-yl)-3-[[2'-(1H-tetrazol-5-yl) biphenyl-4-yl]methyl]-3H-imidazo[4,5-b] pyridine) is a potent inhibitor of angiotensin type 1 (AT1 ) receptors in rabbit aorta and human recombinant AT1 receptors. In the isolated rabbit thoracic aorta, KR31080 caused a nonparallel shift to the right of the concentration-response curves to angiotensin II (All) with decreased maximal response (pD'2 = 10.1 ± 0.1), but had no effect on the contractile response induced by norepinephrine. KR31080 inhibited specific [125 I]AII binding to rabbit aortic membranes (AT, receptors) and [125 I][Sar1 , Ile8 ]AII binding to human recombinant AT1 receptors in a concentration-dependent manner with IC50 values of 0.84 ± 0.08 nM and 1.92 ± 0.15 nM, respectively, but did not inhibit specific [125 I)AII binding to bovine cerebellum membranes (ÀT2 receptors). In the Scatchard analysis, KR31080 interacted with rabbit aortic AT1 receptors in a competitive manner, similar to losartan. These results demonstrate that KR31080 is a potent and AT1 selective angiotensin receptor antagonist which exerts a competitive antagonism in the [125 I]AII binding assay and insurmountable AT1 receptor antagonism in the functional study. 相似文献
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G P Gerrits A A Haagen R A De Abreu L A Monnens F J Gabre?ls F J Trijbels A L Theeuwes J M van Baal 《Clinical chemistry》1988,34(7):1439-1442
Disturbances in the metabolism of purines and pyrimidines in neurologically affected patients can be reflected by aberrant concentrations of nucleosides and nucleobases in cerebrospinal fluid (CSF). However, normal values, especially for children at different ages, are lacking. We collected 1000 specimens of CSF from subjects ranging in age from newborn to 18 years, who were undergoing a diagnostic lumbar puncture for several clinical indications. Of these, 78 samples could be used retrospectively as a reference according to our criteria. The analyses were performed with a modified HPLC procedure. None of the substances shows age-dependency except uridine and uric acid. Uridine increases with age, and uric acid increases with age in boys older than 12 years. 相似文献
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Melatonin is a pineal hormone that regulates the human cycle of sleep and wakefulness. Plasma melatonin levels were investigated in patients with obstructive sleep apnoea syndrome (OSAS). In total, 20 patients with OSAS and 11 healthy controls were studied. OSAS patients were tested twice: on the night of diagnostic polysomnography and the night of continuous positive airway pressure (CPAP) titration. Controls were tested on one occasion. Plasma melatonin levels were determined at 23:00 h (light period), at 02:00 h (dark period) and at 06:00 h (light period) in patients and control subjects using the radioimmunoassay method. The control subjects showed a nocturnal melatonin peak value at 02:00 h (70.6+/-14 pg.mL(-1)). However, this nocturnal melatonin peak was absent in the OSAS patients. The highest melatonin value was found in OSAS patients on the night of diagnosis, at 06:00 h (49.3+/-36.8 pg.mL(-1)). It was found that the melatonin level in OSAS patients at 06:00 h was significantly lower in the night of titration (35.6+/-37.9 pg.mL(-1)) than in the diagnosis night. However, the melatonin levels at either 23:00 h or 02:00 h in OSAS patients did not differ significantly when comparing levels in the night of diagnostic polysomnography (23:00 h: 31.6+/-29.8 pg.mL(-1); 02:00 h: 47.4+/-33.8 pg.mL(-1)) with levels in the night of CPAP titration (23:00 h: 20.2+/-10.3 pg.mL(-1); 02:00 h: 37.7+/-27.5 pg.mL(-1)). Patients with obstructive sleep apnoea syndrome have an abnormal melatonin secretion pattern. The absence of a nocturnal serum melatonin peak could be partially related to the difficulty that these patients have in achieving a normal sleep-wakefulness pattern. 相似文献
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Pedro Magno José Loureiro Alexandre Marques Pedro Farto E Abreu Machado Candido Paulo Leal Victor M Gil 《Revista portuguesa de cardiologia》2007,26(10):1033-1042
Ischemic stroke occurs in 0.2-0.4% of patients undergoing left heart catheterization, and is responsible for 5-10% of the mortality associated with the procedure. The main predisposing factors for this complication are female gender, complex atherosclerotic plaques in the ascending aorta, and peripheral arterial disease. The possibility of timely intervention with reperfusion therapy supports close clinical monitoring during the immediate post-catheterization period. The cardiologist should be familiar with the various types of stroke reperfusion therapy and its indications according to the time interval between catheterization and the stroke. The decision should be discussed with neurology and neuroradiology. 相似文献
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Detection of chromosomes and estimation of aneuploidy in human spermatozoa using fluorescence in-situ hybridization 总被引:11,自引:0,他引:11
The development and application of fluorescence in-situ hybridization
(FISH) has opened the way for comprehensive studies on numerical chromosome
abnormalities in human spermatozoa. FISH can be rapidly applied to large
numbers of spermatozoa and thus overcomes the major limitation of
karyotyping spermatozoa after penetration of zona-free hamster oocytes. The
simultaneous hybridization of two or more chromosome-specific probes to
spermatozoa and subsequent detection of the bound probes using different
fluorescent detection systems enables two or more chromosomes to be
localized simultaneously in the same spermatozoon and provides a technique
for undertaking reasonable estimates of aneuploidy. The most commonly used
probes are those which bind to the centromeric region of specific
chromosomes. Most studies to date have concentrated on estimating
aneuploidy in spermatozoa from normospermic men, although reports are
beginning to appear on aneuploidy in spermatozoa from subfertile and
infertile men. Multi- probe FISH studies have generally reported disomy
(hyperhaploidy) estimates of 0.05-0.2% per chromosome. There is preliminary
evidence that some chromosomes such as X, Y and 21 are predisposed towards
higher rates of non-disjunction during spermatogenesis. There are also
suggestions of inter-donor variability in aneuploidy frequencies for
specific chromosomes, although this requires confirmation in larger
studies. While FISH is clearly a powerful technique that has many
applications in reproductive medicine, it must also be realized that it
does have limitations and the technology itself is still evolving and has
yet to be fully validated on spermatozoa.
相似文献
10.
Deng L Yang M Fründ S Wessel T De Abreu RA Tischfield JA Sahota A 《Molecular genetics and metabolism》2001,72(3):260-264
We have examined the mutational basis of adenine phosphoribosyltransferase (APRT, EC 2.4.2.7) deficiency (MIM 102600) in a patient of Polish origin who has been passing 2,8-dihydroxyadenine (DHA) stones since birth, but has considerable residual enzyme activity in lymphocyte extracts. The five exons and flanking regions of APRT were amplified by PCR and then sequenced. A single T insertion was identified at the intron 4 splice donor site (TGgtaa to TGgttaa:IVS4+2insT) in one allele from the proband, his mother, and brother. A G-to-T transversion in exon 5 (GTC-to-TTC:c.448G>T, V150F) was identified in the other allele, and this mutation was also present in one allele from the father and the paternal grandmother. Tru91 and AvaII digestions of PCR products spanning exons 4 and 5, respectively, confirmed the mutations. The mother was heterozygous for an intragenic TaqI site, but all other family members were homozygous for the presence of this site. IVS4+2insT, located on the allele containing the TaqI site, has been identified previously in several families from Europe, suggesting a founder effect, but the substitution in exon 5 is a novel mutation. IVS4+2insT is known to result in complete loss of enzyme activity, and our results suggest that V150F produces an enzyme that is nonfunctional in vivo but has considerable residual activity in vitro. 相似文献