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61.
M. Abdellah Alaoui Jamali Ming-biao Yin Alessandra Mazzoni Issam Bankusli Youcef M. Rustum 《Cancer chemotherapy and pharmacology》1989,25(2):77-83
Summary The effect ofN-(3,4-dimethoxyphenyl)N-methyl-2-(naphthyl)-m-dithiane-2-propylamine hydrochloride (RO11-2933), an analog of the calcium channel blocker tiapamil, on doxorubicin (DOX)-induced cytotoxicity and DNA damage in human ovarian cancer cells sensitive and resistant to DOX was investigated. A2780-DX2, A2780-DX3, and A2780-DX6 cell sublines were characterized by 7-, 26-, and 48-fold resistance after 2 h DOX exposure and 30-, 50-, and 500-fold resistance after 72 h DOX exposure, respectively. Increased drug efflux resulting in a lower intracellular drug accumulation, decreased DOX-induced DNA single-strand breaks (DNA SSBs), and rapid DNA repair correlated with the degree of resistance. In addition, DNA SSBs were rapidly repaired within 8 h in A2780-DX3 cells, whereas no significant repair of DNA SSBs was observed in sensitive cells. In comparison with verapamil, RO11-2933 was found to reverse DOX resistance at lower and nontoxic concentrations (2 M as compared with 10 M verapamil). This reversion was complete in cells with a low degree of resistance (A2780-DX1 and A2780-DX2) but partial in highly resistant cells (A2780-DX3 and A2780-DX6), and continuous exposure to RO11-2933 was essential for optimal reversal of drug resistance. Interestingly, RO11-2933 was found to inhibit the repair of DNA SSBs induced by DOX but not those induced by X-ray. These results suggest that the potentiation of DNA SSBs and the specific inhibition of DNA repair by RO11-2933 in multidrug-resistant cells could be of particular value in overcoming MDR in the clinic.Abbreviations RO11-2933
N-(3,4-dimethoxyphenethyl)-N-methyl-2-(2-naphthyl)-m-dithiane-2-propylamine hydrochloride
- DOX
doxorubicin-HCl
- SSBs
single-strand breaks
- MDR
multidrug resistance
This work was supported in part by CA 18420 and CA 21071 相似文献
62.
Demonstration of an antigen common to several varieties of neoplasia 总被引:21,自引:0,他引:21
63.
Dr. David Lo Christina R. Reilly Linda C. Burkly Jenefer DeKoning Terri M. Laufer Laurie H. Glimcher 《Immunologic research》1997,16(1):3-14
Ten years ago, we proposed a model for thymus function in which thymic epithelial cells are primarily responsible for imprinting
major histocompatibility complex (MHC)-restricted specificity, and bone marrow-derived macrophages or dendritic cells are
responsible for the induction of self-tolerance. Since then, transgenic and knockout models have allowed for a dissection
of thymic stromal components in vivo, leading to a new understanding of their specialized functions. We have determined that
with regard to class II-restricted CD4 T-cell development, two distinct subsets of thymic epithelium help shape the repertoire:
Cortical epithelium appears solely responsible for positive selection, whereas a fucose-bearing subset of medullary epithelium
is specialized for negative selection. This absolute separation of positive and negative selection into two distinct spatial
and temporal compartments leads to a much simpler view of the process of repertoire selection. Finally, a novel view of the
function of the thymic medulla is discussed. 相似文献
64.
Summary. Nested polymerase chain reaction (PCR) amplifying the morphological transforming region II (mtrII) of cytomegalovirus (CMV)
has been shown to be useful in the detection of CMV DNA in bone marrow transplant (BMT) recipients. However, there has never
been any report on mutation hot spots and subtypes of this open reading frame. Using primers derived from sequences upstream
and downstream of mtrII (ORF 79), CMV DNA from peripheral blood leukocytes (PBL) and conventional CMV culture of 16 BMT recipients
were amplified by PCR, cloned into pUC118, and sequenced. The amino acid sequences were predicted using the standard triplet
code. The DNA sequences obtained from direct amplification of CMV in PBL obtained from the 16 patients were 100% identical
to the corresponding ones obtained by amplification of CMV DNA extracted from conventional CMV culture. Within mtrII (ORF
79), hot spot single base mutations were observed at positions +40 (G→A), +123 (A→G), +213 (T→C), and +219 (T→C). However,
because of third base degeneracy, only amino acid 14 was changed from valine to isoleucine in the predicted protein of 13
patients. This corresponded to the hot spot mutation at position +40 (GTC→ATC), while the rest were silent mutations. An insertion
of 3 bases (ACG) was observed in the CMV DNA of 10 patients at positions +91 to +93, leading to a threonine insertion at amino
acid 31 in these patients. For patient no. 147 there was a 65 bp deletion in the CMV DNA amplified later in the course of
BMT as compared with that early in the course. This gave rise to a frame shift mutation and a change of more than 70% in the
predicted amino acid sequence of the protein.
Accepted October 14, 1998 Received May 20, 1998 相似文献
65.
Alessandra Renieri Maria Teresa Bassi Lucia Galli Jing Zhou Marisa Giani Mario de Marchi Andrea Ballabio 《Human mutation》1994,4(3):195-198
Alport's syndrome is characterized clinically by a nonimmune glomerulopathy, often accompanied by sensorineural hearing loss and lens abnormalities, frequently due to mutations in the COL4A5 gene. The association of AS with diffuse leiomyomatosis, a benign proliferation of smooth muscle that occurs most often in the esophagus, trachea, and female genitalia, has been reported. Recently, a deletion involving both the COL4A5 and COL4A6 genes has been reported in four unrelated families. We report an additional case with Alport's syndrome associated with leiomyomatosis carrying a deletion of both COL4A5 and COL4A6 genes. A detailed characterization of the genomic region involved in the deletion event has been performed. Our results demonstrate that the deletion removed exon l of COL4A5 and exons l and 2 of COL4A6. © 1994 Wiley-Liss, Inc. 相似文献
66.
67.
R C Porter P Lo D E Low A E Simor A McGeer S Scriver T C Moore C Goldman M Skulnick 《Journal of clinical microbiology》1993,31(10):2794-2795
The BACTEC PLUS 26 (NR26) (Becton Dickinson, Towson, Md.) high-volume blood culture bottle replaced the less expensive smaller-volume NR6A bottle in our hospital. An audit carried out several months after their introduction revealed that only 17.5% of the NR26 bottles received the required blood volume. Several audits and educational programs were required in order to achieve a compliance rate of > 60%. 相似文献
68.
Louis Journeau Marc-Antoine Pistorius Ulrique Michon-Pasturel Marc Lambert Francois-Xavier Lapébie Alessandra Bura-Riviere Philippe de Faucal Patrick Jego Quentin Didier Cécile Durant Geoffrey Urbanski Baptiste Hervier Claire Toquet Christian Agard Olivier Espitia 《Autoimmunity reviews》2019,18(5):476-483
69.
Previous literature presents discordant results on the relationship between physiological and subjective sexual arousal in women. In this study, the use of hierarchical linear modeling (HLM) revealed a significant concordance between continuous measures of physiological and subjective sexual arousal as assessed during exposure to erotic stimuli in a laboratory setting. We propose that past studies that have found little or no association between the two measures may have been in part limited by the methodology and statistical analyses employed. 相似文献
70.
Vitale C Cornoldi A Gebara O Silvestri A Wajngarten M Cerquetani E Fini M Ramires JA Rosano GM 《Menopause (New York, N.Y.)》2005,12(5):552-558
OBJECTIVE: The lack of a beneficial long-term cardiovascular effect of hormone therapy and the early incidence of cardiovascular adverse events observed in recent randomized studies have been related to a heightened inflammatory effect of hormone therapy. DESIGN: We evaluated the effect of different postmenopause therapies on inflammatory markers and endothelial function in 205 postmenopausal women before and after therapy. RESULTS: all postmenopausal women, estrogens alone increased plasma levels of C-reactive protein (CRP) but decreased all other markers of inflammation including interleukin-6 (IL-6) (CRP: +75% +/- 11%, intracellular adhesion molecule: -21% +/- 4%, vascular cell adhesion molecule: -15% +/- 6%, E-selectin: -18% +/- 4%, s-thrombomodulin -10.5% +/- 3.7%, IL-6 -14% +/- 6%; percent changes, P < 0.01 compared with baseline). Raloxifene and tibolone did not significantly affect the overall inflammatory milieu. In a minority of patients, estrogen-progestogen associations and tibolone increased IL-6 levels and induced unfavorable changes on inflammation markers (CRP: +93% +/- 8%, intracellular adhesion molecule: -3% +/- 2%, vascular cell adhesion molecule: -5% +/- 2%, E-selectin: +6% +/- 2%, s-thrombomodulin: +5% +/- 2%, IL-6: +12% +/- 4%; percent changes compared with baseline). Patients with increased IL-6 levels were older and had a longer time since menopause. In all patients except those with increased IL-6 levels, hormone therapy improved endothelial function, whereas tibolone and raloxifene did not significantly change endothelial function compared with baseline. A worsening of endothelial function was detected in patients with increased IL-6 levels during therapy. CONCLUSIONS: Postmenopausal hormone therapy is associated with decreased vascular inflammation; however, in patients with a longer time since menopause, postmenopause hormone therapy may increase inflammation and worsen endothelial function. These unfavorable vascular effects may be detected by an elevation in IL-6 levels and by a lack of improvement in endothelial function. 相似文献