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41.
Neurofibromatosis 2 (NF2) is an inherited cancer syndrome resulting from
mutations in the NF2 tumor suppressor gene. Analysis of NF2 mutations has
revealed some general genotype-phenotype correlations. Severe disease has
been associated with mutations that produce a premature termination while
more mild disease has been associated with missense mutations. Here, we
provide experimental proof for these genotype-phenotype correlations by
demonstrating that nonsense mutations fail to produce stable merlin protein
while missense mutations result in the generation of merlin proteins
defective in negative growth regulation. This inability to suppress cell
growth may result from defects in the function of merlin at several levels,
including failure to form an intramolecular complex. Based on these
findings, we propose a model for merlin growth suppression that provides a
framework for analyzing NF2 patient mutations and merlin function.
相似文献
42.
JS Pooni Dr DWL Hukins PF Harris RC Hilton KE Davies 《Surgical and radiologic anatomy : SRA》1986,8(3):175-182
Posterior and anterior heights, cross-sectional area and shape were measured for all the intervertebral discs in four spines from elderly human cadavers. Disc height was a minimum at the T4-5 level; thoracic discs were less wedge-shaped than those in the cervical and lumbar regions. Cross-sectional area increased from the cranial to caudal extremity; at the L5-S1 level the nucleus pulposus occupied a high proportion of this area. Cervical discs tended to have an elliptical cross-sectional shape, thoracic discs were more circular and lumbar discs tended to have an elliptical cross-section which was flattened or re-entrant posteriorly. This shape distribution was quantified by defining a shape index which had a maximum value of 1 for a circular cross-section. Orientations of the reinforcing fibres in the outer lamellae of the anterior annulus fibrosus were measured from 27 discs by X-ray diffraction. For these measurements, C3-4, T7-8 and L2-3 were chosen as representative of cervical, thoracic and lumbar discs. The fibre tilt, with respect to the axis of the spine, was significantly less in the cervical discs (at 65 degrees) than in the thoracic and lumbar discs (about 70 degrees). These findings are interpreted in relation to differing functional requirements and possible mechanisms of failure in the cervical, thoracic and lumbar regions of the spine in the light of current knowledge on the biomechanics of the intervertebral disc. 相似文献
43.
44.
Detecting pre-ovulatory luteinizing hormone surges in urine 总被引:2,自引:1,他引:2
Kesner JS; Knecht EA; Krieg EF Jr; Wilcox AJ; O'Connor JF 《Human reproduction (Oxford, England)》1998,13(1):15-21
The study objectives were to determine (i) if pre-ovulatory luteinizing
hormone (LH) surges, undetected in urine by two immunoradiometric assays
(IRMA), were detectable by an ultrasensitive immunofluorometric assay
(IFMA) and (ii) the influence of creatinine adjustment on the detection and
timing of the urinary LH surges. Daily urine specimens were contributed by
healthy 25-36 year old volunteers during 14 ovulatory menstrual cycles for
an epidemiological study conducted in 1983-1985. Specimens were selected as
having been previously assayed by two IRMA without consistently detecting
LH surges. These urine specimens were remeasured using an IFMA and adjusted
for creatinine concentration. IFMA measurements revealed unambiguous LH
surges in all cycles. Adjusting IRMA urinary LH values for creatinine
concentrations revealed previously undetected LH surges in four of eight
cycles. Creatinine adjustment also altered the timing of IRMA and IFMA LH
surges by 1-5 days. These results demonstrate an IFMA that detects pre-
ovulatory LH surges in unpreserved, frozen urine from cycles where such
surges were previously undetectable. Further, creatinine adjustment can
markedly affect detection and timing of the onset and peak of the urinary
LH surge. While our analysis suggests that this adjustment improves the
validity of the LH measure, this requires further investigation.
相似文献
45.
46.
D Naor B Bonavida R A Robinson I N Shibata D E Percy D Chia E V Barnett 《European journal of immunology》1976,6(11):783-789
NZB and NZB/W mice have reduced anti-sheep red cell (SRC) and 2,4,6-trinitrophenyl-plaque-froming cell (TNP-PFC) responses with age after injection of either the thymus-dependent antigen TNP-SRC or the thymus-independent antigen TNP-mouse red cells (MRC). However, the thymus-dependent response diminished much faster than the thymus-independent response. As a consequence, young New Zealand mice have a higher anti-TNP response after injection of TNP-SRC than after injection of TNP-MRC, while old New Zealand mice have a higher anti-TNP response after injection of TNP-MRC than after injection of TNP-SRC. The PFC avidity of NZB/W mice injected with TNP-SRC diminished with age, while the PFC avidity of mice injected with TNP-MRC did not change with agrc or TNP-SRC. Old NZB/W mice had few spontaneous anti-MRC-PFC. The number of anti-MRC PFC in old mice was increased 4 to 10 times after injection with either TNP-SRC or TNP-MRC. It is suggested that surveillance mechanisms are responsible for suppressing the autoimmune response to modified self-antigens. The unregulated immune system of NZB and NZB/W mice appears to be an expression of impairment of such a hypothetical surveillance mechanism. 相似文献
47.
Locomotion defects, together with Pins, regulates heterotrimeric G-protein signaling during Drosophila neuroblast asymmetric divisions 下载免费PDF全文
Heterotrimeric G proteins mediate asymmetric division of Drosophila neuroblasts. Free Gbetagamma appears to be crucial for the generation of an asymmetric mitotic spindle and consequently daughter cells of distinct size. However, how Gbetagamma is released from the inactive heterotrimer remains unclear. Here we show that Locomotion defects (Loco) interacts and colocalizes with Galphai and, through its GoLoco motif, acts as a guanine nucleotide dissociation inhibitor (GDI) for Galphai. Simultaneous removal of the two GoLoco motif proteins, Loco and Pins, results in defects that are essentially indistinguishable from those observed in Gbeta13F or Ggamma1 mutants, suggesting that Loco and Pins act synergistically to release free Gbetagamma in neuroblasts. Furthermore, the RGS domain of Loco can also accelerate the GTPase activity of Galphai to regulate the equilibrium between the GDP- and the GTP-bound forms of Galphai. Thus, Loco can potentially regulate heterotrimeric G-protein signaling via two distinct modes of action during Drosophila neuroblast asymmetric divisions. 相似文献
48.
Tan JA George E Tan KL Chow T Tan PC Hassan J Chia P Subramanium R Chandran R Yap SF 《Clinical and experimental medicine》2004,4(3):142-147
Abstract
β-thalassemia is the most-common genetic disorder of hemoglobin synthesis in Malaysia, and about 4.5% of the population are
heterozygous carriers of the disorder. Prenatal diagnosis was performed for 96 couples using the Amplification Refractory
Mutation System and Gap-Polymerase Chain Reaction. We identified 17 β-globin defects-initiation codon for translation (T-G),
-29 (A-G), -28 (A-G), CAP +1 (A-C), CD 8/9 (+G), CD 15 (G-A), CD 17 (A-T), CD 19 (A-G), Hb E (G-A), IVS1-1 (G-T), IVS1-5 (G-C),
CD 41/42 (-CTTT), CD 71–72 (+A), IVS2-654 (CT), poly A(A-G), 100-kb Gγ(Aγδβ)° and 45-kb Filipino deletions. The 192 β-alleles studied comprised Chinese (151 patients), Malay (21), Orang Asli from
East Malaysia (15), Filipino (1), Indian (1), Indonesian Chinese (2), and Thai (1). In the Chinese, 2 β-globin defects at
CD 41/42 and IVS2-654 were responsible for 74% of β-thalassemia. β-mutations at CD 19, IVS1-1 (G-T), IVS1-5, poly A, and hemoglobin
E caused 76% of the hemoglobin disorders in the Malays. The Filipino 45-kb deletion caused 73.3% of bthalassemia in the Orang
Asli. Using genomic sequencing, the rare Chinese β-mutation at CD 43 (G-T) was confirmed in 2 Chinese, and the Mediterranean
mutation IVS1-1 (G-A) was observed in a Malay β-thalassemia carrier. The β-globin mutations confirmed in this prenatal diagnosis
study were heterogenous and 65 (68%) couples showed a different globin defect from each other. The use of specific molecular
protocols has allowed rapid and successful prenatal diagnosis of β-thalassemia in Malaysia. 相似文献
49.
The role of platelets in mesangial localization has been studied in Lewis rats following a single intravenous injection of colloidal carbon 32 mg/100 g body weight. Following carbon injection there was an abrupt thrombocytopenia (peripheral platelet count at 10 min 165 +/- 107 X 10(3)/mm3). Temporary sequestration of platelets in lung, liver and spleen was demonstrated using quinacrine-labelled platelets. Carbon was quantitated in blood, lung, liver and spleen by digestion and spectrophotometry and in glomerular mesangium by particle counting of histological sections under oil-immersion microscopy. In thrombocytopenic rats (busulphan 17.5 mg/kg weight) blood carbon levels (up to 1 h after injection) were higher than normal controls (P less than 0.01) and mesangial carbon content at 24 h was significantly increased (P less than 0.01). No significant alteration in mononuclear phagocytic function was detected at 24 h. In platelet-restored thrombocytopenic rats, (busulphan-treated, infused with homologous platelets) blood and mesangial carbon levels were decreased towards normal values. These findings show that (1) platelets are involved in the initial removal of carbon from the blood (2) mesangial localization is related to blood levels and (3) platelet numbers affect both these parameters. The finding of increased mesangial deposition in thrombocytopenic rats may have significance for immune complex glomerulonephritis where platelet numbers may be low due to persistent platelet activation. 相似文献
50.