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11.
12.
Imai K Zhu Y Revy P Morio T Mizutani S Fischer A Nonoyama S Durandy A 《Clinical immunology (Orlando, Fla.)》2005,115(3):277-285
Autosomal recessive form of hyper-IgM syndrome type 2 (AR-HIGM2) is secondary to mutations affecting both alleles of AICDA gene encoding activation-induced cytidine deaminase, characterized by defects of immunoglobulin class switch recombination (CSR) and somatic hypermutation (SHM) in most of the patients. We herein report the immunological phenotype of seven patients carrying a single heterozygous R190X mutation in AICDA. Variable defect in in vivo CSR inherited as an autosomal dominant (AD) trait strongly suggests that this heterozygous AICDA mutation causes HIGM (AD-HIGM2). In AD-HIGM2 B cells, CSR was consistently found impaired in vitro. However, in contrast to AR-HIGM2, the CSR-induced double-stranded DNA breaks in the switch region of IgM heavy chain gene were detected. The SHM frequency in V regions of IgM heavy chain gene in B cells was normal in all (but one patient). The characteristics of the AD-HIGM2 phenotype indicate that the AID C-terminal region may be involved in DNA repair machinery required for CSR. 相似文献
13.
Kazuya Takeda Shuhei Sakakibara Kazuo Yamashita Daisuke Motooka Shota Nakamura Marwa Ali El Hussien Jun Katayama Yohei Maeda Masanobu Nakata Shigeyuki Hamada Daron M. Standley Masaki Hayama Takashi Shikina Hidenori Inohara Hitoshi Kikutani 《The Journal of allergy and clinical immunology》2019,143(3):1163-1175.e15
14.
Vif is dispensable for simian immunodeficiency virus (SIV) replication in some cells, termed permissive (i.e., CEM-SS), but not in others, termed non-permissive (i.e., H9, CEMx174, and peripheral blood lymphocytes). Non-permissive cells express the RNA editing enzyme, APOBEC3G. To determine whether vif mRNA could be alternatively spliced, a mutation altering the putative vif splice acceptor site (SA1) was introduced into SIV(mac239) (SIV(Deltavif-SA)). Despite three consensus splice acceptor sites nearby SA1, SIV(Deltavif-SA) did not efficiently generate alternatively spliced vif mRNA. SIV(Deltavif-SA) was growth attenuated in CEMx174 and H9 cells but not in CEM-SS cells. Following SIV(Deltavif-SA), but not SIV(mac239), infection in either H9 or CEMx174 cells viral cDNA contained numerous G to A mutations; no such differences were observed in CEM-SS cells. This pattern is consistent with mutations generated by APOBEC3G in the absence of Vif. Therefore, efficient splicing of SIV vif mRNA is tightly controlled and requires the SA1 site. 相似文献
15.
Tokuhiro Ishihara Yoshimi Yamashita Yoshiko Okuzono Tadaaki Yokota Mutsuo Takahashi Toshiaki Kamei Fumiya Uchino Noboru Matsumoto Shiro Miwa Hisaichi Fuji Takeshi Kozaki 《Ultrastructural pathology》1985,8(1):13-23
By light and electron microscopy, we observed foamy cells in the spleens from a patient with hemolytic anemia due to red cell adenosine deaminase (ADA) overproduction, a patient with rheumatoid arthritis (RA) treated with gold, and patients with idiopathic thrombocytopenic purpura (ITP)
The foamy cells associated with red cell ADA overproduction were essentially similar to Gaucher-like cells described in patients with thalassemia, and it was suggested that the accelerated destruction of red cells was one of the factors responsible for the development of foamy cells. Foamy cells in ITP and RA were closely associated with an increased destruction of platelets in the spleen. Morphologic transitions between phagocytosed platelets and myelinlike materials were traced in these disorders. In RA, however, foamy cells were heterogeneous from an ultrastructural standpoint, with different cytoplasmic inclusions. In addition to myelinlike materials, dense bodies, vacuoles with flocculent materials, and gold were noted in most of foamy cells. As gold compounds are known to inhibit lysosomal enzymes, we surmise that an acquired disturbance in lysosomal digestion is partially responsible for the accumulation of intermediate metabolites.
In the pathogenesis of foamy cells associated with blood cell dyscrasia, the accelerated destruction of blood cells and/or acquired disorders in catabolic pathways within the macrophages are suggested to be the underlying mechanism of an intralysosomal accumulation of incompletely degraded cellular debris. 相似文献
The foamy cells associated with red cell ADA overproduction were essentially similar to Gaucher-like cells described in patients with thalassemia, and it was suggested that the accelerated destruction of red cells was one of the factors responsible for the development of foamy cells. Foamy cells in ITP and RA were closely associated with an increased destruction of platelets in the spleen. Morphologic transitions between phagocytosed platelets and myelinlike materials were traced in these disorders. In RA, however, foamy cells were heterogeneous from an ultrastructural standpoint, with different cytoplasmic inclusions. In addition to myelinlike materials, dense bodies, vacuoles with flocculent materials, and gold were noted in most of foamy cells. As gold compounds are known to inhibit lysosomal enzymes, we surmise that an acquired disturbance in lysosomal digestion is partially responsible for the accumulation of intermediate metabolites.
In the pathogenesis of foamy cells associated with blood cell dyscrasia, the accelerated destruction of blood cells and/or acquired disorders in catabolic pathways within the macrophages are suggested to be the underlying mechanism of an intralysosomal accumulation of incompletely degraded cellular debris. 相似文献
16.
M. Nicotra N. Bottini M. Grasso A. Gimelfarb N. Lucarini E. Cosmi E. Bottini 《American journal of reproductive immunology (New York, N.Y. : 1989)》1998,39(4):266-270
PROBLEM: We have investigated the possible role of adenosine deaminase (ADA) genetic polymorphism in human fertility through a comparative study of couples with recurrent spontaneous abortion (RSA) and healthy puerperae. METHOD OF STUDY: Adenosine deaminase phenotype has been determined in 209 women with repeated episodes of unexplained spontaneous abortion (RSA) and their husbands, as well as in 115 healthy pregnant women from the population of Rome. An independent sample of 286 puerperae along with their newborn infants in the population of Penne was also studied. RESULTS: The proportion of carriers of ADA*2 allele, which is associated with the lowest enzymatic activity, is lower among women with RSA than among healthy pregnant women from the same population of Rome. Preliminary observations suggest a protective effect of ADA*2 against the development of autoantibodies in RSA. Such an effect seems to be mediated by an interaction with ABO blood groups. In the population of Penne the proportion of women carrying ADA*2 allele is higher among those who have had two or more previously born children than among women with only one or no children. CONCLUSIONS: The data suggest that women carrying the ADA*2 allele are better protected against the spontaneous loss of embryos and have a higher fertility rate. 相似文献
17.
Muscle-type phosphofructokinase deficiency (PFKD) causes a hemolytic disorder and exertional myopathy in humans and dogs.
In humans, PFKD is accompanied by a disturbed calcium homeostasis and associated adenine nucleotide dysregulation, which may
potentiate the erythroenzymopathy associated with this inherited disorder. This study shows that canine PFKD also manifests
these erythrocyte abnormalities. Compared to normal, healthy red cells, PFK-deficient erythrocytes contain lower concentrations
of ATP and higher concentrations of IMP and calcium, the latter as per a calcium indicator dye. Adenosine monophosphate deaminase
(AMPD) enriched 5000-fold from canine erythrocytes adsorbs to immobilized calcium–calmodulin and the interaction between these
two proteins activates AMPD through a K
mapp effect. This behavior is similar to that of the human erythrocyte enzyme and provides a potential contributing mechanism
for accelerated adenine nucleotide turnover in canine PFKD. We propose that adenine nucleotide replacement strategies could
benefit the erythroenzymopathy in human and canine PFKD and that the dog model of this disorder is an appropriate vehicle
for further elucidating this hypothesis. 相似文献
18.
Corban-Wilhelm H Becker G Bauder-Wüst U Greulich D Debus J 《Clinical and experimental medicine》2003,3(3):150-156
The efficacy of single and combination suicide gene therapy was evaluated using a Herpes simplex virus thymidine kinase/ganciclovir system and Escherichia coli cytosine deaminase/5-fluorocytosine system on the rat prostate tumor cell line R3327 AT-1. The wild-type R3327 AT-1 cell line was transfected with a bifunctional fusion gene CDglyTK, which had the advantage that the resulting R3327 AT-1/CDglyTK cell line has the same amount of cytosine deaminase and thymidine kinase molecules. The percentage of viable R3327 AT-1/CDglyTK cells after 96 h incubation with 0.1 micro g/ml ganciclovir or 10 micro g/ml 5-fluorocytosine were 85% and 52% of controls, respectively. The cell viability when both suicide genes systems were activated was 43%. For in vivo analysis, Copenhagen rats were injected subcutaneously with R3327 AT-1 or R3327 AT-1/CDglyTK cells and treated with 30 mg/kg ganciclovir, 500 mg/kg 5-fluorocytosine, or both prodrugs together. A survival of 83% with the thymidine kinase/ganciclovir and 57% with the CD/5-FC could be observed. Only co-administration of thymidine kinase- and cytosine deaminase-specific prodrugs resulted in a 100% recurrence-free survival of the Copenhagen rats with a Dunning R3327 AT-1/CDglyTK prostate tumor and showed an additive cytotoxic effect. Calculation of the degree of activation and the potential of activation can be used to predict the success of a suicide gene therapy. In our case, the cytosine deaminase/5-fluorocytosine system had a low degree of activation (value 40), which is also found in the low response to 5- fluorocytosine in vivo (57% tumor free). 相似文献
19.
本文观察到腺苷脱氨酶抑制剂EHNA对离体灌流大鼠心脏氧反常性损伤有明显的作用,此外还发现在缺氧期(无氧灌流30分钟)EHNA也表现出明显的保护作用,心脏收缩幅度的降低和静息张力的升高均显著低于对照组。表明在缺氧期也可能有自由基的产生。 相似文献
20.
目的 :探讨大剂量阿糖胞苷 ( HDAC)治疗儿童急性白血病的效果和不良反应。 方法 :应用 HDAC治疗 3例急性髓细胞白血病 (每次 2 .0 g/m2 ,每 12 h1次 ,共 6次为一个疗程 )和 4例高危型急性淋巴细胞白血病 (每次1.0 g/m2 ,每 12 h1次 ,共 8次为一个疗程 )共 16个疗程 ,九个疗程在 HDAC结束后使用惠尔血 ( 2~ 3μg/kg)皮下注射 ,连续 10~ 14天。 结果 :6例按计划完成 HDAC治疗 ,并继续用常规方案治疗者 ,在 2 0~ 42个月的随访期内无病生存 ,1例 AL L- L3型在一个疗程 HDAC后出现中枢神经系统白血病复发 ,骨髓仍缓解 ,7个月后放弃治疗 .骨髓严重抑制和感染是最主要的不良反应 ,加用惠尔血可使粒细胞缺乏的持续时间缩短 ,感染发生率降低。 结论 :以 HDAC为主的联合化疗方案可安全地用于儿童急性白血病的强化治疗 ,对降低复发、提高无病生存率有积极意义 相似文献