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51.
Sustained localized expression of ligand for the activating NKG2D receptor impairs natural cytotoxicity in vivo and reduces tumor immunosurveillance 总被引:11,自引:0,他引:11
Oppenheim DE Roberts SJ Clarke SL Filler R Lewis JM Tigelaar RE Girardi M Hayday AC 《Nature immunology》2005,6(9):928-937
Upregulation of the inducible gene products MICA (human) and Rae-1 (mouse) may promote tumor surveillance and autoimmunity by engaging the activating receptor NKG2D on natural killer (NK) cells and T cells. Nevertheless, sustained expression of MICA by tumors can also elicit NKG2D downregulation, perhaps indicating 'immunoevasion'. Investigating this paradox, we report here that constitutive Rae-1epsilon transgene expression in normal epithelium elicited local and systemic NKG2D downregulation, generalized but reversible defects in NK cell-mediated cytotoxicity and mild CD8(+) T cell defects. The extent of NKG2D downregulation correlated well with the incidence and progression of cutaneous carcinogenesis, emphasizing the utility of NKG2D as a marker of tumor resistance. Thus, NKG2D engagement is a natural mediator of immunosurveillance, which can be compromised by locally sustained ligand expression but potentially restored by innate immune activation. 相似文献
52.
In the present study the effect of antidepressant drugs on the density of dopamine D2/D3 receptors in the rat forebrain was examined using autoradiography, since this technique provides the appropriate anatomical
resolution. Male Wistar rats were treated with three various antidepressant drugs: imipramine, citalopram and mianserin in
a dose of 10 mg/kg p.o., acutely (single dose) or repeatedly (twice a day for 14 days). To estimate the distribution of D2/D3 receptors, we chose following radioligands: [3H]raclopride, a non-selective antagonist of D2/D3 receptors, and [3H]quinpirole, a non-selective D2/D3 agonist. When [3H]raclopride was used as a radioligand, no significant differences in the density of D2/D3 receptors were observed after administration of the investigated drugs. However, following repeated administration of imipramine,
citalopram and mianserin, a significant increase in the binding of [3H]quinpirole was observed, both in the nucleus caudatus and nucleus accumbens septi. In some cases the increase of [3H]quinpirole binding was also observed after acute treatment with antidepressant drugs. Thus, using an agonist as a radioligand,
we were able to see upregulation of dopamine D2/D3 receptors in the rat forebrain following administration of antidepressant drugs, which might be interpreted as the biochemical
correlative for the postsynaptic dopamine D2/D3 receptor supersensitivity observed in previous behavioral studies.
Received: 13 February 1998 / Accepted: 13 November 1998 相似文献
53.
Anna Scattone Gilda Caruso Andrea Marzullo Domenico Piscitelli Mattia Gentile Lucia Bonadonna Giuseppe Balducci Maria Cristina Digilio Alessandro Jenkner Francesca Diomedi Camassei Renata Boldrini Pietro Nazzaro Lucio Pollice Gabriella Serio 《Fetal and pediatric pathology》2003,22(4):323-341
Deletion 22q11.2 is a chromosomal abnormality detected in young patients with clinical manifestations of the DiGeorge/velocardiofacial syndrome. Conotruncal heart defects are also associated with del22q11.2. An association of these cardiac malformations with neoplasias has been observed. Our series includes two cases of malignancies, a hepatoblastoma and a renal-cell carcinoma, arising in children with complex cardiac malformations. The aim of the study was to determine if the deletion at 22q11.2 was present and could be responsible for both pathological processes. Del22q11.2 was identified in both cases. Comparative genomic hybridization revealed terminal gains on chromosomes 1q and Xq and terminal loss on 1p in the hepatoblastoma, and gains in 1p, 12q, 16p, 20q, 22q, and whole chromosome 19 and loss of Xq in the renal-cell carcinoma. Our results confirm a common genetic basis for cardiac malformations, and del22q11.2 presents a risk factor for the development of pediatric tumours. 相似文献
54.
Allen L Seligson Brian K Campion Jason W Brown Ron C Terry Renata Kucerova Martina Bienova Marian Hajduch Milos Sovak 《Drug development research》2003,59(3):292-306
Nonsteroidal antiandrogens (AA) cannot be topically used for androgenetic alopecia (AGA) because of systemic resorption. A new class of androgen receptor (AR) suppressors designed for safe topical treatment of AGA was synthesized from (3‐amino‐2‐hydroxy‐2‐methyl‐N‐(4‐nitro‐3‐trifluoromethyl)phenyl) propanamide (BP‐34), to contain perfluoroalkyl moieties. The trifluoromethyl derivative (fluridil) at 10 μM decreased expression of the AR in LNCaP human cells by 95%, its serum half‐life was 6 h; it decomposes hydrolytically to BP‐34 and trifluoroacetic acid. Acute intraperitoneal maximum tolerated dose (MTD) of fluridil in mice is 270–300 mg/kg/d and the subacute MTD is 450 mg/kg/d. The oral LD50 in mice was 2,872 mg/kg in males, 2,232 mg/kg in females, and >2,500 mg/kg in rats. Fluridil solution in isopropanol was not cutaneously absorbed in rabbits, did not sensitize or show any phototoxic or photoallergic effects on guinea pig skin, and demonstrated no skin irritation potential in rabbits and humans. Fluridil solid induced only slight and reversible eye irritancy in rabbits and displayed no cytotoxicity to rabbit corneal fibroblasts in vitro. Fluridil demonstrated no significant mutagenicity potential by Ames method. In a double‐blind study, 43 males with AGA, Norwood grade II to Va, used topical 2% fluridil in isopropanol or the vehicle daily for 12 months. Anagens (growing hairs) increased in the fluridil group from 76% to 89%. All hematological and biochemistry values remained within normal range, including testosterone, which varied but seasonally. No fluridil or its decomposition product (BP‐34) was detected in serum. No adverse side effects were reported. Drug Dev. Res. 59:292–306, 2003. © 2003 Wiley‐Liss, Inc. 相似文献
55.
56.
Hellen Silva Cintra Juliana Castro Dourado Pinezi Graziella Dias Pinheiro Machado Gustavo Moura de Carvalho Ana Terra Silva Carvalho Thalles Eduardo Dias dos Santos Ricardo Duarte Marciano Renata de Bastos Ascen?o Soares 《Disease markers》2013,35(6):701-710
The purpose of this study was to evaluate the association between ATM, TP53 and MDM2 polymorphisms in prostate cancer patients and morbidity after radiotherapy. The presence of ATM (rs1801516), TP53 (rs1042522, rs1800371, rs17878362, rs17883323, and rs35117667), and MDM2 (rs2279744) polymorphisms was assessed by direct sequencing of PCR fragments from 48 patients with histologically proven prostate adenocarcinoma and treated with external beam radiation. The side effects were classified according to the Radiation Therapy Oncology Group (RTOG) score. The results showed no association between clinical characteristics and the development of radiation toxicities (P > 0.05). The C>T transition in the position 16273 (intron 3) of TP53 (rs35117667) was significantly associated with the risk of acute skin toxicity (OR: 0.0072, 95% CI 0.0002–0.227, P = 0.003). The intronic TP53 polymorphism at position 16250 (rs17883323) was associated with chronic urinary toxicity (OR: 0.071, 95%CI 0.006–0.784, P = 0.032). No significant associations were found for the remaining polymorphisms (P > 0.05). The results show that clinical characteristics were not determinant on the developing of radiation sensitivity in prostate cancer patients, and intronic TP53 polymorphisms would be associated with increased acute and chronic radiation toxicities. These observations corroborate the importance of investigating the genetic profile to predict adverse side effects in patients undergoing radiotherapy. 相似文献
57.
J. Renata Ochocka Monika Asztemborska Danuta Sybilska Wioletta Langa 《Pharmaceutical biology》2013,51(5):395-399
The enantiomeric contents of monoterpenes have been determined in essential oils from the following species: Pinus cembra, Pinus nigra, Pinus pinaster, Pinus montana, Pinus sylvestris, Abies alba and Abies sibirica. A gas chromatographic method with a formamide solution of a-cyclodextrin as a stationary phase was applied for the separation and determination of enantiomers. 相似文献
58.
Leonardo Silva de Araujo Fernanda Carvalho de Queiroz Mello Nidai de Bárbara Moreira da Silva Janaina Aparecida Medeiros Leung Silvia Maria Almeida Machado Isabela Gama Sardella Renata de Moraes Maciel Maria Helena Féres Saad 《Clinical and Vaccine Immunology : CVI》2014,21(4):552-560
The PstS1 antigen is highly immunogenic, principally when combined with CFP10 during both latent and active TB infection. In the present study, a selected pstS1 gene fragment was cloned, fused with CFP10, and expressed in Escherichia coli. The product [PstS-1(285-374):CFP10] was compared to the recombinant fused RD1 (region of deletion 1) protein (ESAT-6:CFP10) in detecting Mycobacterium tuberculosis infection in 108 recent contacts of pulmonary tuberculosis (TB) cases, considering a positive tuberculin skin test (TST) to be the baseline. The release of gamma interferon (IFN-γ) in 22-h whole-blood and 5-day lymphocyte stimulation assays primed with each antigen was determined. All contacts were clinically followed for up to 1 year, and 87% of the tuberculin skin test-positive (TSTpositive) patients accepted preventative treatment. Concerning the IFN-γ response to PstS-1(285-374):CFP10 in the 22-h and 5-day assays, a slight increase in contact-TSTpositive detection was observed (23/54 and 26/54) compared to the level seen with the RD1 protein (18/54 and 24/54) whereas in the TSTnegative group, similarly lower numbers (≤5/48) of responders were achieved for both antigens, except for RD1 in the 5-day assay (8/48). By combining the IFN-γ responders to both antigens in the 5-day assays, slightly higher increases in positivity were found in the TSTpositive (32/54) and TSTnegative (10/48) groups. Two of 12 untreated TSTpositive contacts progressed to active TB and were concordantly positive in all assays, except for one contact who lacked positivity in the RD1 5-day assay. We demonstrated for the first time that PstS-1(285-374):CFP10 slightly increased contact positivity and detection of active disease progression, suggesting its potential application as a TB infection marker. 相似文献
59.
60.
Carolina Degen Meotti Glaura Plates Letycia Lopes Chagas Nogueira Renata Anselme da Silva Karoline Silva Paolini Elias Moreira Nunes Fred Bernardes Filho 《Anais brasileiros de dermatologia》2014,89(2):332-333
Cutaneous larva migrans is a pruritic dermatitis due to the inoculation of helminths
larvae in the skin, and it often occurs in children in tropical and subtropical
areas. The authors describe an atypical case of cutaneous larva migrans in a 11
year-old child with scalp involvement, an unusual topography for this lesion. 相似文献