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91.
Huang TL Bacchi CJ Kode NR Zhang Q Wang G Yartlet N Rattendi D Londono I Mazumder L Vanden Eynde JJ Mayence A Donkor IO 《International journal of antimicrobial agents》2007,30(6):555-561
A series of 32 piperazine-linked bisbenzamidines (and related analogues) were analysed for their in vitro and in vivo trypanocidal activity against a drug-sensitive strain of Trypanosoma brucei brucei and a drug-resistant strain of Trypanosoma brucei rhodesiense. The compounds showed similar potencies against both strains. The most potent compounds were bisbenzamidines substituted at the amidinium nitrogens with a linear pentyl group (8, inhibitory concentration for 50% (IC50) = 1.7–3.0 nM) or cyclic octyl group (17, IC50 = 2.3–4.6 nM). Replacement of the diamidine groups with diamidoxime groups resulted in a prodrug (22) that was effective orally against T. b. brucei-infected mice. Three compounds (7, 11 and 15) provided 100% cure when administered parenterally. The results indicate that the nature of the substituents at the amidinium nitrogens of bisbenzamidines strongly influence their trypanocidal activity. 相似文献
92.
Caroline Bret Dirk Hose Thierry Reme Anne-Catherine Sprynski Karène Mahtouk Jean-François Schved Philippe Quittet Jean-François Rossi Hartmut Goldschmidt Bernard Klein 《British journal of haematology》2009,145(3):350-368
Syndecan-1 is a proteoglycan that concentrates heparin-binding factors on the surface of multiple myeloma cells, and probably plays a major role in multiple myeloma biology. As heparan sulphate and chondroitin sulphate are the bioactive components of syndecan-1, we analysed the signature of genes encoding 100 proteins involved in synthesis of these chains, i.e. from precursor uptake to post-translational modifications, using Affymetrix microarrays. The expression of enzymes required for heparan sulphate and chondroitin sulphate biosynthesis was shown to increase in parallel with syndecan-1 expression, throughout the differentiation of memory B cells into plasmablasts and normal bone marrow plasma cells. Sixteen genes were significantly different between normal and malignant plasma cells, nine of these genes – EXT2, CHSY3 , CSGALNACT1 , HS3ST2 , HS2ST1 , CHST11 , CSGALNACT2 , HPSE , SULF2 – encode proteins involved in glycosaminoglycan chain synthesis or modifications. Kaplan–Meier analysis was performed in two independent series of patients: B4GALT7 , CSGALNACT1 , HS2ST1 were associated with a good prognosis whereas EXT1 was linked to a bad prognosis. This study provides an overall picture of the major genes encoding for proteins involved in heparan sulphate and chondroitin sulphate synthesis and modifications that can be implicated in normal and malignant plasma cells. 相似文献
93.
Michel Jourdan Thierry Reme Hartmut Goldschmidt Geneviève Fiol Véronique Pantesco John De Vos Jean-François Rossi Dirk Hose Bernard Klein 《British journal of haematology》2009,145(1):45-58
The survival of malignant plasma cells is a key event in disease occurrence, progression and chemoresistance. Using DNA-microarrays, we analysed the expression of genes coding for 58 proteins linked with extrinsic and intrinsic apoptotic pathways, caspases and inhibitor of apoptosis proteins. We considered six memory B cells (MBC), seven plasmablasts (PPC), seven bone marrow plasma cells (BMPC) and purified myeloma cells (MMC) from 92 newly-diagnosed patients. Forty out of the 58 probe sets enabled the separation of MBC, PPC and BMPC in three homogeneous clusters, characterized by an elevated expression of TNFRSF10A, TNFRSF10B, BCL2A1, CASP8, CASP9 and PMAIP1 genes for MBC, of FAS, FADD, AIFM1, BIRC5, CASP CASP2, CASP3 and CASP6 for PPC and of BCL2, MCL1, BID, BIRC3 and XIAP for BMPC. Thus, B cell differentiation was associated with change of expression of pro-apoptotic and anti-apoptotic genes. Regarding MMC, the major finding was TRAIL upregulation that might be counteracted by a high osteoprotegerin production by BM stromal cells and a decreased expression of FAS, APAF1 and BNIP3 compared to normal BMPC. Out of the 40 genes, CASP2 and BIRC5 expression in MMC had adverse prognosis in two independent series of previously-untreated patients. 相似文献
94.
Fumiya Miyamura Shinichi Kako Hiroko Yamagami Ken Sato Miki Sato Kiriko Terasako Shun-ichi Kimura Hideki Nakasone Satoko Aoki Shinya Okuda Rie Yamazaki Kumi Oshima Kentaro Yoshinaga Takakazu Higuchi Junji Nishida Toshio Demitsu Akihiro Kakehashi Yoshinobu Kanda 《International journal of hematology》2009,90(3):397-401
Only some carriers of human T cell lymphotropic virus type I (HTLV-1) develop adult T cell leukemia/lymphoma (ATLL) after a long latency period, and an association has been reported between chronic refractory eczema, known as infective dermatitis, and young-onset ATLL. A 25-year-old female developed ATLL and underwent allogeneic hematopoietic stem cell transplantation (HSCT) in non-remission. She had chronic refractory eczema and corneal injury at the onset of ATLL. Remission of ATLL was achieved, and the HTLV-1 proviral load decreased after HSCT. In addition, her pre-existing eczema and corneal injuries almost disappeared. More than a year has passed since the transplantation was performed, and she has had no recurrence of either ATLL or lesions in the skin and eye. Her clinical course suggests a possible association between skin and eye lesions and HTLV-1 infection. Changes in the immunological condition after HSCT might play a key role. Special attention is needed when HTLV-1 carriers develop eye or skin lesions. 相似文献
95.
Sachiko Kanaji Taisuke Kanaji Miho Honda Sachie Nakazato Kazuo Wakayama Yoshitomi Tabata Shoichiro Shibata Hisashi Gondo Ikuko Nakamura Koichi Node Masanori Miura Masaharu Miyahara Takashi Okamura Fumio Nagumo Shoichiro Ohta Kenji Izuhara 《International journal of hematology》2009,89(1):71-75
Coagulation factor V (FV) deficiency is a rare bleeding disorder characterized by low coagulant and antigen levels of FV with
bleeding symptoms ranging from mild to severe. Only a limited number of mutations have been reported because of the large
size of the factor V gene (F5) as well as the low prevalence. In this study, we have identified four novel mutations in F5 in five unrelated patients with congenital FV deficiency. All the patients, including two with undetectable FV activity,
were asymptomatic and were found to have prolonged prothrombin time and activated partial thromboplastin time during preoperative
screening or routine examinations. All four mutations found in this study are either missense or in-frame deletion. This is
in contrast with previous reports of a high frequency of mutations introducing premature termination codons in inherited FV
deficiency. Missense mutations of F5 might produce a mild phenotype and are not frequently diagnosed. Although FV deficiency is a very rare disorder with a predicted
incidence of one in 1 million, this study suggests that the numbers of F5 mutations, especially missense mutations, are higher than estimated. 相似文献
96.
Rapid eye movement sleep decreases between 10 and 30 days postnatally in the rat. The pedunculopontine nucleus is known to modulate waking and rapid eye movement sleep, and pedunculopontine nucleus neurons are thought to be hyperpolarized by noradrenergic input from the locus coeruleus. The goal of the study was to investigate the possibility that a change in alpha-2 adrenergic inhibition of pedunculopontine nucleus cells during this period could explain at least part of the developmental decrease in rapid eye movement sleep. We, therefore, recorded intracellularly in 12-21 day rat brainstem slices maintained in oxygenated artificial cerebrospinal fluid. Putative cholinergic vs. non-cholinergic pedunculopontine nucleus neurons were identified using nicotinamide adenine dinucleotide phosphate diaphorase histochemistry and intracellular injection of neurobiotin (Texas Red immunocytochemistry). Pedunculopontine nucleus neurons also were identified by intrinsic membrane properties, type I (low threshold spike), type II (A) and type III (A+low threshold spike), as previously described. Clonidine (20 microM) hyperpolarized most cholinergic and non-cholinergic pedunculopontine nucleus cells. This hyperpolarization decreased significantly in amplitude (mean+/-S.E.) from -6.8+/-1.0 mV at 12-13 days, to -3.0+/-0.7 mV at 20-21 days. However, much of these early effects (12-15 days) were indirect such that direct effects (tested following sodium channel blockade with tetrodotoxin (0.3 microM)) resulted in hyperpolarization averaging -3.4+/-0.5 mV, similar to that evident at 16-21 days. Non-cholinergic cells were less hyperpolarized than cholinergic cells at 12-13 days (-1.6+/-0.3 mV), but equally hyperpolarized at 20-21 days (-3.3+/-1.3 mV). In those cells tested, hyperpolarization was blocked by yohimbine, an alpha-2 adrenergic receptor antagonist (1.5 microM). These results suggest that the alpha-2 adrenergic receptor on cholinergic pedunculopontine nucleus neurons activated by clonidine may play only a modest role, if any, in the developmental decrease in rapid eye movement sleep. Clonidine blocked or reduced the hyperpolarization-activated inward cation conductance, so that its effects on the firing rate of a specific population of pedunculopontine nucleus neurons could be significant. In conclusion, the alpha-2 adrenergic input to pedunculopontine nucleus neurons appears to consistently modulate the firing rate of cholinergic and non-cholinergic pedunculopontine nucleus neurons, with important effects on the regulation of sleep-wake states. 相似文献
97.
Sasaki M Saito T Kubo N Saito T Ikoma A Tamemoto H Saito M Kawakami M Ishikawa SE 《Diabetes research and clinical practice》2006,71(3):339-344
The present study was undertaken to determine accumulation of risk factors in acute myocardial infarction during two periods of 2002 and 1990-1991. We collected 173 and 153 patients with acute myocardial infarction in 2002 and 1990-1991, respectively, and analyzed the history of multiple risk factors, including diabetes mellitus, impaired glucose tolerance, hyperlipidemia, hypertension and obesity, and laboratory findings. The numbers and their percentages of all the risk factors increased in 2002 compared with 1990-1991. According to plasma glucose level, the patients who had type 2 diabetes mellitus, and impaired fasting glucose or impaired glucose tolerance had increased markedly from 41 to 65%. Multiple accumulation of risk factors had increased during the last one decade, and only one or no risk factor per se was not the case in the patients with acute myocardial infarction. Hyperlipidemia and hypertension became fairly controlled in the patients, but not hyperglycemia in type 2 diabetes mellitus in the period of 2002. These findings may indicate that increased multiple accumulation of risk factors accelerates the occurrence of acute myocardial infarction in 2002 as compared to 1990-1991. 相似文献
98.
Kumi Oshima Yoshinobu Kanda Yasuhito Nanya Masatsugu Tanaka Chiaki Nakaseko Shingo Yano Shin Fujisawa Hiroyuki Fujita Akira Yokota Satoshi Takahashi Heiwa Kanamori Shinichiro Okamoto 《Annals of hematology》2013,92(2):255-260
While renal comorbidity is generally defined by the serum creatinine level, the creatinine clearance rate (Ccr) is a more accurate indicator of renal function. Therefore, we retrospectively assessed how mildly reduced renal function as defined based on Ccr affects the outcome after allogeneic hematopoietic stem cell transplantation (HSCT). Patients who underwent allogeneic HSCT at the eight institutes of the Kanto Study Group for Cell Therapy were included in this study. Based on the corrected Ccr, patients were classified into group 0 (n?=?440, ?≥?90 mL/min/1.73 m2), group 1 (n?=?56, 60–89 mL/min/1.73 m2), or group 2 (n?=?11, 30–59 mL/min/1.73 m2). Therefore, 67 patients were considered to have mild renal impairment, whereas only 2 had a serum creatinine level higher than 1.2 mg/dL. Twenty-eight patients required hemodialysis after HSCT, with 5.5, 5.4, and 9.1 % in groups 0, 1, and 2, respectively (p?=?0.65). The incidence of non-relapse mortality (NRM) was higher in group 2, although these differences were not statistically significant probably due to the small sample size (23.7, 28.2, and 47.2 % at 3 years, p?=?0.20). In conclusion, NRM may be associated with mildly reduced renal function before allogeneic HSCT, which cannot be detected by measurement of the serum creatinine level alone. 相似文献
99.
Hideki Takeuchi Hiroyuki Takei Kazushige Futsuhara Takashi Yoshida Makoto Kojima Toshihiro Kai Toshio Tabei 《International journal of clinical oncology / Japan Society of Clinical Oncology》2014,19(1):68-73
Background
Because of its superior efficacy to tamoxifen, anastrozole has been widely used in Japan as an adjuvant treatment for postmenopausal, hormone-responsive breast cancer patients. However, anastrozole may affect bone in Japanese patients similar to its effects in Western patients. The aim of this study is to evaluate the rate of bone fracture and bone mineral density (BMD) during anastrozole treatment in Japanese patients.Patients and methods
In this study, 350 postmenopausal women with hormone-responsive, stage I to IIIA breast cancer were enrolled and scheduled to receive adjuvant anastrozole treatment for up to 5 years. Patients underwent clinical examination for bone fractures and annual measurement of BMD during treatment.Results
After a median follow-up of 33.0 months, bone fractures occurred in 1.8 %. Annual fracture rates were 0.3 and 1.2 % during the first and second year, respectively. The overall median BMD significantly decreased, measuring 87.5, 84.3, and 83.5 % at baseline and after 1 and 2 years, respectively. Musculoskeletal disorders were the most common (26.1 %), and hot flashes were the second most common adverse event (7.9 %). Severe adverse events occurred in 5.5 % of all the cases.Conclusions
In this interim analysis, the bone fracture rate was lower than that in the Western population despite a significant reduction of BMD after 2 years of treatment with anastrozole. Adjuvant anastrozole treatment was well tolerated in Japanese postmenopausal women with breast cancer. Long-term follow-up data is necessary to elucidate the racial disparities of the safety profile of anastrozole. 相似文献100.