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41.
Alain Bernheim 《Molecular oncology》2010,4(4):309-322
The role of acquired chromosomal rearrangements in oncogenesis (cytogenomics) and tumor progression is now well established. These alterations are multiple and diverse and the products of these rearranged genes play an essential role in the transformation and growth of cancer cells. The validity of this assumption is demonstrated by the development of specific inhibitors or antibodies that eliminate tumoral cells by targeting some of these changes. Imatinib, an inhibitor of the tyrosine kinase ABL, the prototype of these targeting drugs, is yielding complete remissions in most CML patients. Knowledge of chromosomal abnormalities is becoming an essential contribution to the diagnosis and prognosis of cancers but also for monitoring minimal residual disease or relapse. The concept of the “cytogenetic uniqueness” of each cancer has resulted in personalized treatment. This investigation will expound upon, besides the recurrent genomic alterations, the numerous products of perverted Darwinian selection at the cellular level. 相似文献
42.
43.
Plasmid-Determined AmpC-Type β-Lactamases 总被引:26,自引:0,他引:26
44.
Differential apoptotic response of J774 macrophages to alumina and ultra-high-molecular-weight polyethylene particles. 总被引:2,自引:0,他引:2
Alain Petit Isabelle Catelas John Antoniou David J Zukor Olga L Huk 《Journal of orthopaedic research》2002,20(1):9-15
We recently identified apoptosis in in vitro wear particle-stimulated macrophages. The recent explosion of interest in apoptosis lies in the fact that it is under positive and negative regulation through evolutionary conserved biochemical pathways. It may also be possible to modulate macrophage apoptosis in the treatment of periprosthetic osteolysis. The purpose of this study was to compare the macrophage response to identically sized particles of alumina ceramic (Al2O3) and ultra-high-molecular-weight polyethylene (UHMWPE) in terms of TNF-alpha release and induction of apoptosis. J774 mouse macrophages were incubated for 0-24 h in the presence of Al2O3 and UHMWPE particles. TNF-alpha release was measured by ELISA; Poly(ADP-ribose)polymerase (PARP) and caspase-3 expression was analyzed by Western blot; DNA fragmentation (DNA laddering) was visualized on agarose gel containing ethidium bromide. Al2O3 particles induced TNF-alpha release after 4 h incubation with concentrations reaching 483 and 800 pg/ml after 24 h with 125 and 250 particles/macrophage, respectively (control = 161 pg/ml) (P < 0.05 vs. control). The same concentrations of UHMWPE particles induced a much larger and significant TNF-alpha release after only 1 h incubation, increasing up to 6250 pg/ml after 24 h (P < 0.05 vs. control). Western blot analysis demonstrated that the active caspase-3 fragment (17 kDa) and the proteolytic PARP fragment (85 kDa) were expressed after 2 h incubation with 125 and 250 Al2O3 particles/macrophage. The active caspase-3 and the PARP fragment had lower expression and appeared after a longer incubation time (8 h) with 125 and 250 UHMWPE particles/macrophage. Finally, DNA fragmentation (DNA laddering) was observed after 16 h with 125 and 250 particles of Al2O3 per macrophage whereas no laddering was induced by UHMWPE particles even after 24 h incubation. This study shows that although both Al2O3 and UHMWPE particles induce TNF-alpha release, this stimulation was much greater (8-10 times higher) with UHMWPE than Al2O3 (P < 0.05 vs. control). As well, the induction of apoptosis, as measured by activation of caspase-3, PARP cleavage and DNA laddering, is different for these two particles, being faster and more important with Al2O3 than UHMWPE. We hypothesize that the ability of Al2O3 to induce macrophage apoptosis may explain the lower TNF-alpha release observed with these particles and explain the differences seen in osteolysis patterns of ceramic-ceramic (CC) vs. metal-polyethylene (Mpe) articulations. In conclusion, apoptosis may be a major internal mechanism to decrease macrophage activity and may be a desired therapeutic endpoint. The identification of an apoptosis-related pathway in the macrophage response to ceramic particles provides crucial data for a rational approach in the treatment and/or prevention of periprosthetic osteolysis. 相似文献
45.
Laurent Garel Josée Dubois Fran?oise Rypens Alain Ouimet Salam Yazbeck 《Journal l'Association canadienne des radiologistes》2004,55(1):39-44
OBJECTIVE: To report on the high incidence of anatomical variants of the origin and course of the internal spermatic vein (ISV) discovered at the time of percutaneous embolization of left varicoceles in a pediatric population. METHODS: We reviewed retrospectively the 65 cases of left varicocele treated by percutaneous embolization (grade II and III) in our institution between 1990 and 2000. The course of the left renal vein (LRV), the origin of the ISV, and the number of ISVs and their pathway were recorded in all cases, according to the B?hren classification. RESULTS: In 37/65 (57%), the ISV was single and arose from a normal LRV (type I). The following variants were encountered: type V--circumaortic LRV 9/65 (14%); type IVb--intrarenal origin of ISV 8/65 (12%); type II--multiple ISV 5/65 (8%); and pelvic collaterals 6/65 (9%). CONCLUSION: Venous anatomical variants are frequently encountered (43%) at the time of left varicocele embolization in children. Such variants often impose some adjustments to the technique of embolization and, at times, hamper the procedure. 相似文献
46.
Alain Gobert Rodolphe Billiras Laetitia Cistarelli Mark J. Millan 《Journal of neuroscience methods》2004,140(1-2):141
Information concerning striatal levels of noradrenaline (NA) remains inconsistent. Here we have addressed this issue using a sensitive method of HPLC coupled to amperometric detection. The NA reuptake-inhibitor, reboxetine, selectively elevated levels of NA versus dopamine (DA), and NA levels were also selectively elevated by the α2-adrenoceptor (AR) antagonist, atipamezole. The actions of atipamezole were mimicked by the preferential α2A-AR antagonist, BRL44408, while JO-1 and prazosin, preferential antagonists at α2C-ARs, caused less marked elevations in NA levels. In contrast to antagonists, the α2-AR agonist, S18616, decreased NA levels and likewise suppressed those of DA. Unilateral lesions of the substantia nigra with 6-hydroxydopamine depleted DA levels without affecting those of NA. Further, the D3/D2 receptor agonist, quinelorane, decreased levels of DA without modifying those of NA. However, the D3/D2 receptor antagonists, haloperidol and raclopride, and the DA reuptake-inhibitor, GBR12935, elevated levels of both DA and NA. Levels of 5-HT (but not of NA or DA) were increased only by the 5-HT reuptake-inhibitor, citalopram. They were decreased by S18616 and prazosin, reflecting the inhibitory and excitatory influence of α2- and α1-ARs, respectively, upon serotonergic pathways. In conclusion, NA in the striatum is derived from adrenergic terminals. Its release is subject to tonic, inhibitory control by α2-ARs, possibly involving both α2A- and α2C-AR subtypes, though their respective contribution requires clarification. A role of dopaminergic terminals in the reuptake of NA likely explains the elevation in its levels elicited by DA reuptake-inhibitors and D3/D2 receptor antagonists. 相似文献
47.
BACKGROUND: Photon energy recovery (PER) is a spectral deconvolution technique validated for scatter removal in patients and phantom studies. The purpose of this study was to examine the impact of PER on left ventricular volume measurement based on myocardial perfusion single photon emission computed tomography (SPECT). METHODS AND RESULTS: SPECT acquisitions were performed by use of a static cardiac phantom and in 25 patients after a rest injection of technetium 99m sestamibi by use of multiple energy windows (126-136, 137-144, and 145-154 keV). Data were successively reconstructed with and without PER, by use of iterative reconstruction and post-processing filtering (Butterworth filter; order, 5; cutoff, 0.30 cycles/pixel). Image contrast was evaluated in reconstructed data, and volumes were calculated by use of QGS. PER increased reconstructed image contrast from 62% +/- 2.7% to 84.3% +/- 5.7% in the phantom studies (P <.0001) and from 49% +/- 2% to 73% +/- 2% in patients (P <.0001). Although it remained underestimated (P <.0001), phantom volume was higher after PER correction compared with uncorrected data (50.9 +/- 0.8 mL vs 44.6 +/- 1 mL, P <.0001). The error in volume measurement was decreased by PER correction (16.6% +/- 1.3% vs 27% +/- 1.7% [uncorrected data], P <.0001). In patients, left ventricular volume increased from 83 +/- 10 mL to 91 +/- 10 mL (P <.0001), and the PER-induced volume increase was correlated with the image contrast increase (r = 0.61, P =.001). Finally, the percentage of volume increase was higher in patients with small left ventricular volumes. CONCLUSIONS: PER has a significant impact on image contrast and left ventricular volume measurement by use of perfusion SPECT. PER improves the accuracy of phantom volume assessment. In patients, volume increase is correlated to image contrast increase and is higher in those with small ventricles. 相似文献
48.
Possible involvement of multiple human cytochrome P450 isoforms in the liver metabolism of propofol 总被引:4,自引:1,他引:3
Guitton J.; Buronfosse T.; Desage M.; Flinois J. P.; Perdrix J. P.; Brazier J. L.; Beaune P. 《British journal of anaesthesia》1998,80(6):788-795
Previous studies of propofol (2,6-diisopropylphenol) pharmacology have
shown that this widely used anaesthetic drug is extensively cleared from
the body by conjugation of the parent molecule or its quinol metabolite. On
the basis of potential influence of propofol on the metabolism of
co-administered agents, many investigators have evaluated the effects of
propofol on cytochrome P450 (CYP) activities. CYP isoforms involved in
propofol metabolism are not defined. In this study, our objective was to
elucidate further the CYP isoforms responsible for the hydroxylation of
propofol. Using microsomes from 12 different human livers, we investigated
CYP isoforms involved in propofol hydroxylase activity, using selective
chemical inhibitors of CYP isoforms, correlation with immunoquantified
specific CYP isoform content, immunoinhibition, and 11 functionally active
human CYP isoforms expressed in a heterologous system (yeast and human B-
lymphoblastoid cells). We found a low variability in the production of the
hydroxylated metabolite of propofol, 2,6-diisopropyl-1,4-quinol. This
activity was mediated by CYP and followed Michaelis-Menten kinetics with
apparent K(M) and Vmax values of 18 microM (95% Cl 15.1- 20.1) and 2.6 nmol
min-1 mg-1 (95% Cl 2.45-2.68) respectively. Part of the propofol
hydroxylase activity was mediated by CYP2C9 in human liver, especially at
low substrate concentration. Moreover, propofol was likely to be
metabolized by additional isoforms such as CYP2A6, 2C8, 2C18, 2C19 and 1A2,
especially when substrate concentrations are high. This low specificity
among CYP isoforms may contribute to the low interindividual variability
(two-fold) and may contribute to the low level of metabolic drug
interactions observed with propofol.
相似文献
49.
In order to define precisely the relation between descending monoaminergic systems and the motor system, we measured in the ventral horn of spinal cord of adult rats the variations of extracellular concentrations of 5-HT, 5-HIAA, DA and MHPG. Measurements were performed during rest, endurance running on a treadmill, and a post-exercise period, with microdialysis probes implanted permanently for 45 days. We found a slight decrease in both 5-HT and 5-HIAA during locomotion with a more marked decrease during the post-exercise period compared to the mean of rest values. In contrast, the concentration of DA and MHPG increased slightly during the exercise and decreased thereafter. These results, when compared with those of a previous study, which measured monoamines in the spinal cord white matter [C. Gerin, D. Bécquet, A. Privat, Direct evidence for the link between monoaminergic descending pathways and motor activity: I. A study with microdialysis probes implanted in the ventral funiculus of the spinal cord, Brain Res. 704 (1995) 191–201], highlight the complex regulation of the release of monoamines that occurs in the ventral horn. 相似文献
50.
Michel A. Ghossain Jean-Noël Buy Alain Ruiz Denis Jacob Catherine Sciot Danile Hugol Dominique Vadrot 《Journal of magnetic resonance imaging : JMRI》1998,8(6):1203-1206
A case of hyperreactio luteinalis in an otherwise normal pregnancy is reported. Ascites was present, but no peritoneal implants or adenopathy were seen. Findings that would have suggested the correct diagnosis are the symmetrical and bilateral pattern of the mass, as well as the rather uniform size of the loculi, which were 1 to 3 cm in diameter. 相似文献