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31.
The GAP-related domain of tuberin, the product of the TSC2 gene, is a target for missense mutations in tuberous sclerosis 总被引:5,自引:0,他引:5
Maheshwar MM; Cheadle JP; Jones AC; Myring J; Fryer AE; Harris PC; Sampson JR 《Human molecular genetics》1997,6(11):1991-1996
Tuberous sclerosis is an autosomal dominant trait in which the
dysregulation of cellular proliferation and differentiation results in the
development of hamartomatous growths in many organs. The TSC2 gene is one
of two genes determining tuberous sclerosis. Inactivating germline
mutations of TSC2 in patients with tuberous sclerosis and somatic loss of
heterozygosity at the TSC2 locus in the associated hamartomas indicate that
TSC2 functions as a tumour suppressor gene and that loss of function is
critical to expression of the tuberous sclerosis phenotype. The TSC2
product, tuberin, has a region of homology with the GTPase activating
protein rap1GAP and stimulates the GTPase activity of rap1a and rab5a in
vitro. Here we show that the region of homology between tuberin and human
rap1GAP and the murine GAP mSpa1 is more extensive than previously reported
and spans approximately 160 amino acid residues encoded within exons 34-38
of the TSC2 gene. Single strand conformation polymorphism analysis of these
exons in 173 unrelated patients with tuberous sclerosis and direct
sequencing of variant conformers together with study of additional family
members enabled characterisation of disease associated mutations in 14
cases. Missense mutations, which occurred in exons 36, 37 and 38 were
identified in eight cases, four of whom shared the same recurrent change
P1675L. Each of the five different missense mutations identified was shown
to occur de novo in at least one sporadic case of tuberous sclerosis. The
high proportion of missense mutations detected in the region of the TSC2
gene encoding the GAP-related domain supports its key role in the
regulation of cellular growth.
相似文献
32.
Mahadevan MM; McIntosh Q; Miller MM; Breckinridge SM; Maris M; Moutos DM 《Human reproduction (Oxford, England)》1998,13(4):979-982
Cryopreservation of human zygotes and embryos has been routinely performed
by in-vitro fertilization clinics for many years. Karran and Legge (1996)
first reported that formaldehyde (FA) present in the cryoprotective
solutions can have a deleterious effect on mouse oocytes. FA is a
cytotoxic, carcinogenic and mutagenic chemical. The effect of FA on mouse
zygotes was investigated. In addition, the concentrations of FA in
propanediol (PROH) obtained from various sources were determined. Pooled
1-cell embryos were dispensed into droplets of modified Ham's F10 or human
tubal fluid containing various concentrations of FA. Since bovine serum
albumin (BSA) may minimize toxicity additional trials were done as above in
the absence of BSA. FA concentration in the standard 1.5 M PROH, from
different sources in water, was measured in the same assay using a standard
curve of 0-100 microM FA. FA in a complex medium had a significant
deleterious effect on embryo development and hatching but only at 1 mM
concentration (P < 0.000001; see Tables I-III). There was no significant
effect of FA at 100 microM. However, in a simple medium even 50 microM FA
decreased embryo hatching. FA was present in 1.5 M PROH from different
sources (range 1.0-35.3 microM concentration). It appears that FA
concentrations do not increase with storage because FA concentrations were
low even after opening and storage for 3 years on the shelf. This suggests
that FA is a contaminant during the manufacturing process and may vary from
manufacturer to manufacturer and batch to batch. Until further studies are
done to confirm the lack of toxicity to embryos during cryopreservation
(with or without FA scavengers) it may be prudent to screen all batches of
cryoprotectants for FA as part of quality control.
相似文献
33.
W. Ollier P. J. W. Venables P. A. Mumford R. N. Maini J. Awad D. Jaraquemada J. D''Amaro H. Festenstein 《Tissue antigens》1984,24(5):279-291
Seventy-seven patients with rheumatoid arthritis were investigated to examine the frequency of HLA antigens and their relationship to clinical and serological manifestations of extra-articular disease. The phenotype frequencies of DR4, DRw53, Bw62 and Cw3 were significantly increased, compared to normal controls, and there were negative associations with DR2 and DR7. The HLA antigen in strongest association with rheumatoid arthritis was DR4 (73.6%) and the relationship with DRw53 appeared to be secondary. The frequency of DR4 rose to 92% in seropositive patients with extra-articular disease manifestations whose serum contained immune complexes. A high frequency of DR4 was also seen in male patients (86%), reaching 100% in the small group of seropositive male patients with immune complexes. It is suggested that extra-articular disease represents a manifestation of severe classical rheumatoid arthritis and is not an 'overlap' syndrome. We propose that the HLA haplotype Cw3-Bw62-Dw4-DR4-DRw53 makes a greater genetic contribution to disease susceptibility in both extra-articular and male rheumatoid arthritis patients than in other subsets of RA. 相似文献
34.
Renal gluconeogenesis and increased glucose utilization in shock 总被引:1,自引:0,他引:1
35.
Comparison of the human and mouse genes encoding the telomeric protein, TRF1: chromosomal localization, expression and conserved protein domains 总被引:11,自引:0,他引:11
36.
37.
38.
Extracranial-intracranial bypass surgery: a critical analysis in light of the International Cooperative Study 总被引:2,自引:0,他引:2
The ability of extracranial-intracranial bypass surgery to alter favorably the natural history of ischemic cerebrovascular disease remains in question. A recently completed prospective randomized multicenter cooperative trial failed to confirm the hypothesis that the procedure prevents further cerebral ischemia in patients with atherosclerotic internal carotid artery or middle cerebral artery disease. We analyze findings of the study in detail, including possible effects on the natural history of the disease beyond the immediate perioperative period. Potential sources of bias that may have unpredictably affected the study are discussed. These include observational bias (patient and therapist not blinded), "randomization-to-treatment" bias (high morbidity after randomization but before operation), and "prerandomization" or allocation bias (patients in the study representing a selected sample of the population with cerebrovascular disease). The extensive analysis of secondary subgroups with small numbers of patients is discussed in light of the statistical methods used. Two particular classes of patients not addressed in the study who might benefit from the procedure are defined. They are patients failing the best available medical therapy and patients with clearly documented hemodynamic compromise. Possible indications for bypass surgery are suggested for the various lesions in light of the trial and of recent reports on the natural history and pathophysiology of ischemic cerebrovascular disease. Selected cases illustrating these indications are presented. 相似文献
39.
Cobb Cory L. Salas-Wright Christopher P. John Rachel Schwartz Seth J. Vaughn Michael Martínez Charles R. Awad Germine Pinedo Miguel Cano Miguel Ángel 《Prevention science》2021,22(3):397-407
Prevention Science - We examined national trends and mental health correlates of discrimination among Latinos in the USA. We used data from two nationally representative surveys based on the... 相似文献
40.
The meta-analysis was performed to assess the efficacy and safety of daily oral L-arginine and phosphodiesterase type 5 inhibitors (PDE5Is) alone or combination in treating patients with erectile dysfunction (ED). We performed a search of randomised controlled trials in the following databases: PubMed, EMBASE and Cochrane Library databases. Four articles including 373 patients were studied. Erectile functions were significantly improved in three therapy groups compared with baseline. Patients who received the combination of L-arginine and PDE5Is showed significant improvement compared to those treated with L-arginine and PDE5Is alone, as assessed by sexual function index (p <0.00001 and p =0.005, respectively) and total testosterone (p <0.00001 and p =0.0007, respectively). Furthermore, patients who treated with PDE5Is alone exhibited the better efficacy than those treated with L-arginine alone in respects of sexual function index (p <0.00001) and total testosterone (p =0.0001). However, the combination of L-arginine and PDE5Is had no obvious difference relative to PDE5Is alone in terms of various adverse events (AEs). Conclusively, compared with monotherapy, the combination of L-arginine and PDE5Is showed a greater improvement of sexual function and total testosterone, and did not significantly increase the AEs. Besides, PDE5Is alone revealed a better effect than those treated with L-arginine alone for patients with ED. 相似文献