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81.
Functional analysis of PTPN11/SHP-2 mutants identified in Noonan syndrome and childhood leukemia 总被引:3,自引:0,他引:3
Niihori T Aoki Y Ohashi H Kurosawa K Kondoh T Ishikiriyama S Kawame H Kamasaki H Yamanaka T Takada F Nishio K Sakurai M Tamai H Nagashima T Suzuki Y Kure S Fujii K Imaizumi M Matsubara Y 《Journal of human genetics》2005,50(4):192-202
Noonan syndrome (NS) is characterized by short stature, characteristic facial features, and heart defects. Recently, missense mutations of PTPN11, the gene encoding protein tyrosine phosphatase (PTP) SHP-2, were identified in patients with NS. Further, somatic mutations in PTPN11 were detected in childhood leukemia. Recent studies showed that the phosphatase activities of five mutations identified in NS and juvenile myelomonocytic leukemia (JMML) were increased. However, the functional properties of the other mutations remain unidentified. In this study, in order to clarify the differences between the mutations identified in NS and leukemia, we examined the phosphatase activity of 14 mutants of SHP-2. We identified nine mutations, including a novel F71I mutation, in 16 of 41 NS patients and two mutations, including a novel G503V mutation, in three of 29 patients with leukemia. Immune complex phosphatase assays of individual mutants transfected in COS7 cells showed that ten mutants identified in NS and four mutants in leukemia showed 1.4-fold to 12.7-fold increased activation compared with wild-type SHP-2. These results suggest that the pathogenesis of NS and leukemia is associated with enhanced phosphatase activity of mutant SHP-2. A comparison of the phosphatase activity in each mutant and a review of previously reported cases showed that high phosphatase activity observed in mutations at codons 61, 71, 72, and 76 was significantly associated with leukemogenesis. 相似文献
82.
Futue direction of three-year educational establishments for students of medical technology 总被引:1,自引:0,他引:1
Mimura K 《Rinsho byori. The Japanese journal of clinical pathology》2003,51(5):467-470
The medical laboratory technologist education currently offered at four state run junior colleges will be upgraded to higher education as all those junior colleges become universities in 2004. It has already been decided that several private junior colleges and vocational schools are to be upgraded to universities as well. Furthermore, the course will not only be offered in undergraduate universities, but also on a postgraduate level, increasing the number of medical laboratory technologists with a master's degree or a doctorate. This reform is perhaps due to a demand for medical laboratory technologists of higher quality because of such social conditions as a highly-sophisticated information society, advancement in healthcare and medicine, and transition from volume to quality. It is also a measure for securing further capacity by seeking adequate human resources because of the declining population in the 18-year-old bracket, due to the declining birth rate. In such a condition, the direction three-year educational establishments must take is to nurture human resources with qualities that compare favorably with university graduates. As ways of accomplishing this, we could focus on practical technological education at vocational schools with the educational period set at four years, or recruit and train university graduates with rudimental abilities, as they do at specialist postgraduate schools. 相似文献
83.
Isao Sakuma Tadashi Yoshino Kunihiro Omonishi Ritsuo Nishiuchi Norihiro Teramoto Hiroyuki Yanai Kunimitsu Kawahara Ichiro Kubonishi Yoshinobu Matsuo & Tadaatsu Akagi 《Pathology international》1999,49(2):103-109
Reed-Sternberg (RS) cells and their mononuclear variants, Hodgkin's (H) cells, are considered to be the neoplastic cells of Hodgkin's disease (HD). The cellular origin of H-RS cells remains the subject of considerable controversy, although most recent papers have claimed that H-RS cells are of B cell origin. Recently, however, it has been reported that some H-RS cells express granzyme B, as observed in cytotoxic T cells and/or natural killer cells, which also express CD95 ligand (FasL/APO-1L). In the present study, the expression of CD95L and granzyme B in H-RS cells of HD was investigated. CD95L was detected in H-RS cells in five of nine HD cases (one case of lymphocyte-rich classical HD, two of these cases of nodular sclerosis type, and two of four cases of mixed cellularity type). All three examined HD cell lines expressed CD95L in the cytoplasm, although cell surface expression was seen only in L428 cells. Three HD cases expressed both CD95L and granzyme B. It was concluded that CD95L is frequently expressed in H-RS cells, which is one of their notable characteristics; albeit it seems to be irrespective of cell lineage. 相似文献
84.
Yoshida K Wada T Sakurai A Wakui K Ikeda S Fukushima Y 《Journal of human genetics》2007,52(8):675-679
A nationwide survey was conducted for predictive genetic testing for late-onset, incurable neurological diseases. A questionnaire
was sent to 125 university hospitals and national hospitals, and was returned by 69% of them. Of the 86 responding hospitals,
63 had genetic counseling clinics and answered the questions concerning predictive testing. Of these, 46 had experienced clients
with an interest in or a request for predictive testing during the period from April 2004 to March 2006. A total of 322 clients
were accumulated, the majority of which were interested in myotonic dystrophy (n = 150), followed by spinocerebellar ataxia (n = 86), spinal and bulbar muscular atrophy (n = 40) and Huntington’s disease (n = 31). Most such clients were counseled by medical doctors, who had the “Japanese Board of Medical Genetics, Clinical Geneticist”
certification, but others, including neurologists, nurses, clinical psychologists or genetic counselors also contributed,
albeit to a lesser extent, to genetic counseling in Japan. Many respondents felt that a multidisciplinary approach by a counseling
team consisting of a clinical geneticist, a neurologist, a genetic nurse, a clinical psychologist and a genetic counselor
had not yet been established. There will be a great need for educated and trained non-medical doctor staff not only to improve
the quality of genetic counseling and psychological support for such clients, but also to conduct the psychosocial research
on Japanese clients requesting predictive genetic testing. 相似文献
85.
Hidetaka Seo Hitomi Masuda Kenjiro Asagoshi Tomoaki Uchiki Shigehisa Kawata Goh Sasaki Takashi Yabuki Shunsuke Miyai Naoki Takahashi Shu-ichi Hashimoto Atsushi Sawada Aki Takaiwa Chika Koyama Kanako Tamai Kohei Kurosawa Ke-Yi Lin Kunihiro Ohta Yukoh Nakazaki 《Cellular & molecular immunology》2021,18(6):1545
Monoclonal antibodies (mAbs) are widely utilized as therapeutic drugs for various diseases, such as cancer, autoimmune diseases, and infectious diseases. Using the avian-derived B cell line DT40, we previously developed an antibody display technology, namely, the ADLib system, which rapidly generates antigen-specific mAbs. Here, we report the development of a human version of the ADLib system and showcase the streamlined generation and optimization of functional human mAbs. Tailored libraries were first constructed by replacing endogenous immunoglobulin genes with designed human counterparts. From these libraries, clones producing full-length human IgGs against distinct antigens can be isolated, as exemplified by the selection of antagonistic mAbs. Taking advantage of avian biology, effective affinity maturation was achieved in a straightforward manner by seamless diversification of the parental clones into secondary libraries followed by single-cell sorting, quickly affording mAbs with improved affinities and functionalities. Collectively, we demonstrate that the human ADLib system could serve as an integrative platform with unique diversity for rapid de novo generation and optimization of therapeutic or diagnostic antibody leads. Furthermore, our results suggest that libraries can be constructed by introducing exogenous genes into DT40 cells, indicating that the ADLib system has the potential to be applied for the rapid and effective directed evolution and optimization of proteins in various fields beyond biomedicine. 相似文献
86.
Hata H Iida M Kashiwazaki S Eda K Hirose H Shiono M Negeshi N Sezai Y 《Artificial organs》2002,26(10):862-867
We contrived a surgical technique for the purpose of improving recent results. From April 1998 to June 2001, 24 patients (aged 60 to 81 years, mean age 71.0 +/- 4.8 years; 11 men, 13 women) underwent replacement of the aortic root and the ascending aorta electively using a Freestyle stentless valve with woven Dacron graft at our institution. The aortic root was replaced first, the distal side of the Dacron graft was then anastomosed, and finally, the proximal side was anastomosed with the outflow of the Freestyle valve. Cardiopulmonary bypass time and cardioplegic time were 297 +/- 83 min and 210 +/- 51 min, respectively. The geometry of the ascending aorta and the diameter mismatch between the dilated ascending aorta and the outflow of the Freestyle valve were fully corrected. There were two early deaths and three late deaths; none valve-related. Postoperative aortogram showed an excellent shape. The mortality, morbidity, and clinical events after the procedure were acceptable. 相似文献
87.
Hayakawa K Aoyagi T Miyaji K Hata M Tanaka S Tanaka A 《Journal of vascular surgery》2002,36(5):946-947
We describe a new vascular access grafting technique featuring end-to-end anastomosis to a deep vein in the forearm, designed to create a functional arteriovenous fistula in the forearm of patients whose subcutaneous veins are not usable for this purpose because of occlusion or attenuation. This new technique offers a valuable option in this setting. 相似文献
88.
One hundred fifteen asymptomatic Japanese volunteers aged from 13 to 76 years were examined by magnetic resonance imaging
(MRI) to evaluate age-related meniscal degeneration and to determine the prevalence of discoid menisci. Each meniscus was
graded in the anterior and posterior portions according to intrameniscal MRI signals. Discoid meniscus was diagnosed if a
bow-tie configuration was noted on three or more contiguous sagittal sections. Meniscal abnormalities on MRI became more prevalent
with age in both men and women. The posterior horn of the medial meniscus showed a significantly higher prevalence of degeneration
than other parts of the meniscus. Discoid menisci were noted in 15 subjects (13% prevalence), always representing the lateral
meniscus. Subchondral changes were observed in 13 subjects more than 40 years old, mostly women, and were located in the medial
compartment. These abnormalities were not correlated with severity of degeneration in the posterior portion of the medial
meniscus. This study demonstrates considerable prevalence of meniscal abnormalities in asymptomatic Japanese subjects.
Received: January 15, 2001 / Accepted: December 13, 2001 相似文献
89.
Mukai T Mera K Nishida K Nakashima M Sasaki H Sakaeda T Nakamura J 《Biological & pharmaceutical bulletin》2002,25(11):1494-1497
Animal models prepared by treatment with toxic compounds such as a carbon tetrachloride have been used to examine drug disposition in hepatic diseases. However, it is possible that these compounds accumulate and cause damage to other organs as they are administered systemically. In this study, we used the liver surface application technique to deliver a toxic compound to the liver to prepare an appropriate animal model in which only the liver is significantly damaged. To restrict the absorption area in the liver, a cylindrical diffusion cell was attached to the liver surface of male Wistar rats. Twenty-four hours after direct addition of carbon tetrachloride to the diffusion cell, plasma levels of glutamic-oxaloacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT), and hepatic malondialdehyde (MDA) concentration were increased, while there were no changes in plasma creatinine or renal MDA level. On the other hand, not only GOT, GPT and hepatic MDA, but also creatinine and renal MDA levels were markedly increased by p.o. and i.p. administration of carbon tetrachloride, suggesting renal damage. These results indicated that the animal models of liver damage prepared by utilizing drug delivery techniques to accumulate toxic compounds in the liver would enable us to investigate the precise effects of hepatic disorder on drug disposition. 相似文献
90.
Hayashi Y Kanzaki J Etoh N Higashino K Goto F Schneider E Kunihiro T 《Journal of neurology》2002,249(12):1683-1688
Nystagmus is a rhythmical rotation of the eyeball. Its characteristics can be defined mathematically by the axis of rotation
and the angular velocity around this axis.
We analysed the axis of rotation for the nystagmus in benign paroxysmal positional vertigo (BPPV) to elucidate its pathophysiology.
Thirteen patients with typical unilateral BPPV participated in the present study. The axis of rotation for the nystagmus was
calculated from images recorded on digital videotape with an infrared CCD camera, using an algorithm that we developed. The
patients' responsiveness to Semont's liberatory maneuver was also assessed.
The results showed that patients could be assigned to one of two groups based on the rotation axis of the nystagmus. In one
group of patients (n = 7; Group A), the axis of rotation was almost vertical to the plane containing the posterior semicircular
canal (PSC) on the presumed affected side. In the other group of patients (n = 6; Group B), it was clustered around the naso-occipital
axis. These results suggest that in the patients in Group A the responsible lesion is confined to the PSC, whereas the pathogenesis
underlying the conditions in those in Group B is considered to be more complicated.
This speculation was reinforced by the difference in responsiveness to Semont's liveratory maneuver. All of the patients in
Group A showed remission of vertigo within 10 days (mean, 2.4 days) after onset of treatment using Semont's liberatory maneuver,
whereas the patients in Group B required
much longer periods of time for remission to occur (mean, 25.7 days).
Our findings lead to the conclusion that by considering the spatial orientation of individual semicircular canals, in the
patients in Group B the pathophysiology is not confined to the PSC, but most probably all three semicircular canals are involved.
Received: 16 January 2002, Received in revised form: 22 May 2002, Accepted: 6 June 2002
Correspondence to Yujiro Hayashi, MD 相似文献