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931.
Dendritic Cells Coinjected with Tumor Cells Treated with an Anticancer Drug to Induce Tumor Rejection 总被引:1,自引:0,他引:1
Naoya Inoue Seiji Yamasaki Kan Kondo Takatsugu Kan Katsuyoshi Furumoto Masayuki Imamura 《Surgery today》2003,33(4):269-276
Purpose: We examined whether bone marrow-derived dendritic cells (DCs) could induce antitumor immunity when a chemotherapeutic drug
was added.
Methods: CT26 (a murine colon cancer cell line syngeneic with BALB/c) and CT26-bearing mice were treated with mitomycin C (MMC) intraperitoneally
(i.p.). Next, mice immunized with a coinjection of DCs and MMC-treated CT26 (i.p.) were given an intradermal inoculation of
CT26. Finally, CT26-bearing mice were treated with MMC (i.p.) with or without DCs, given peritumorally.
Results: Although the inoculated tumor was not rejected in the control mice, CT26 was rejected in 50% of the mice injected with MMC
alone. Apoptosis was observed in the MMC-treated CT26 cells in vitro and in vivo. Immunization with DCs and apoptotic CT26
cells, but not with apoptotic CT26 alone, gave protection against tumor challenge in 7 of 13 mice. A significantly higher
level of cytotoxic T-cell activity and interferon-γ production was seen in the protected mice. When MMC (i.p.) treatment was
followed by peritumoral DC injection in the CT26-bearing mice, remarkable therapeutic effects were observed.
Conclusion: DCs can collaborate with chemotherapy-induced apoptotic tumor cells and elicit improved antitumor immunity, probably through
the acquisition of tumor-associated antigens from apoptotic tumor cells.
Received: January 7, 2002 / Accepted: September 3, 2002
Acknowledgments. We thank Dr. Kazuo Kinoshita for his useful advice on using flow cytometry. This research was partly supported by the Ministry
of Education, Culture, Sports, Science and Technology (No. 11671160).
Reprint requests to: S. Yamasaki 相似文献
932.
933.
R Whelan C Kim M Chen J Leiter M M Grunstein H Hakonarson 《The European respiratory journal》2004,24(4):559-567
Interleukin (IL)-1beta is a pleiotropic, pro-inflammatory cytokine that has been importantly implicated in driving the inflammatory response and resultant changes in airway smooth muscle (ASM) responsiveness in asthma. IL-1beta belongs to a family of molecules, known as the IL-1 axis, which exert both pro- and anti-inflammatory effects. Since dysregulation of IL-1 axis molecules may be critical in the pathobiology of asthma, the present study examined the expression and activation of both the inhibitory and stimulatory IL-1 axis molecules in human ASM cells and their roles in modulating cytokine and immunoglobulin (Ig)E immune complex (IgE cx)-mediated changes in rabbit ASM constrictor and relaxant responsiveness. The results demonstrate the following. 1) Pre-treatment of isolated rabbit tracheal rings with the inhibitory IL-1 axis members, IL-1 receptor antagonist and IL-1 type-II receptor abrogated both IL-5- and IgE cx-induced changes in ASM responsiveness. 2) Administration of IL-5, IL-1beta and IgE cxs to human ASM cells increased mRNA and protein expressions of both stimulatory and inhibitory IL-1 axis molecules. 3) The time course of IL-5-induced IL-1 axis molecule expression preceded that of both IL-1beta and IgE immune cxs. Collectively, these findings suggest that modulation at the level of the interleukin-1 axis of molecules may have significant therapeutic potential in the treatment of asthma. 相似文献
934.
Jung-Won Park Joo-Young Yang Cheol-Woo Kim Kyu-Sang Kim Chein-Soo Hong 《Annals of allergy, asthma & immunology》2006,97(4):551-556
BACKGROUND: Previous studies reported that early diagnosis and avoidance therapy are the most important factors for prevention of permanent lung impairment; however, few studies have evaluated the long-term prognosis of reactive dye-induced occupational asthma (RD-OA). OBJECTIVE: To evaluate the long-term outcomes of RD-OA. METHODS: Methacholine airway hyperresponsiveness (AHR) and lung functions were evaluated and compared in 26 patients with RD-OA at the time of diagnosis and after complete avoidance of the causative agents. Patients with continued (n = 13) or remitted (n = 6) AHR were further monitored for up to a mean +/- SD of 8.7 +/- 1.8 years. RESULTS: The AHR resolved in 10 (38%) of 26 patients a mean +/- SD of 2.2 +/- 1.3 years after complete avoidance of RDs; however, prebronchodilator forced expiratory volume in 1 second (FEV1) values were not different. Levels of IgE specific to the RD-human serum albumin complex were markedly decreased at first follow-up in 5 RD-atopic patients from whom paired serum samples were compared (P = .02). The AHR disappeared in an additional 5 patients and improved in 4 by the second follow-up. The FEV1 values also improved compared with diagnosis and first follow-up levels. Favorable prognosis was associated with early diagnosis of RD-OA and complete avoidance of the causative agent. No association was found with smoking history, latent periods, the presence of RD specific IgE, baseline provocation concentration that caused a decrease in FEV1 of 20%, or FEV1. CONCLUSIONS: Early diagnosis and avoidance therapy are the most important prognostic factors in RD-OA. The AHR and lung function of patients with RD-OA can sometimes be recovered steadily and slowly through avoidance measures. 相似文献
935.
Eun-Jung Choi Byung-Duk Ahn Jae-Il Lee Jung-Wook Kim 《Journal of oral pathology & medicine》2007,36(4):250-251
We report a case of rare multiple internal resorptions. Etiology of multiple internal resorptions is unknown. Interestingly, the patient had an atopic dermatitis, which is possibly related to multiple and rapid internal resorptions. 相似文献
936.
Jiang He Mary Rusckowski Yi Wang Shuping Dou Xinrong Liu Surong Zhang Guozheng Liu Donald J. Hnatowich 《Molecular imaging and biology》2007,9(1):17-23
Objective Pretargeting with radioactivity has significantly improved tumor to normal tissue radioactivity ratios over conventional antibody
imaging in both animal studies and clinical trials. This laboratory is investigating DNA analogues such as phosphorodiamidate
morpholinos (MORFs) for pretargeting using technetium-99m (99mTc) for detection. However, the unique properties of fluorescence activation and quenching combined with oligomers with their
unique properties of hybridization may be particularly useful when used together for pretargeting with optical detection.
The use of linear fluorophore-conjugated oligomer duplexes have been little used in animals, and to our knowledge, have not
previously been considered for pretargeting applications.
Methods A MORF/cDNA pair was selected such that when hybridized, the fluorescence of the Cy5.5-conjugated 25 mer MORF (Cy5.5–MORF25)
is inhibited with a BHQ3-conjugated 18 mer complementary DNA (BHQ3–cDNA18). The short BHQ3–cDNA18 was selected to dissociate
in the presence of a long cMORF25 in the pretargeted tumor, thus releasing the inhibitor from the Cy5.5 emitter. In this manner,
the Cy5.5 fluorescence will be inhibited everywhere but in the target. The dissociation was first examined in vitro by adding the duplex to the cMORF25 both in solution and immobilized on polystyrene microspheres and by surface plasmon resonance
(SPR). Thereafter, biotinylated cMORF25 immobilized on streptavidin polystyrene microspheres were administered intramuscularly
in one thigh of hairless SKH-1 mice as target while an identical weight of the identical microspheres but without the cMORF25
was administered in the contralateral thigh as control. The animals then received IV the Cy5.5–MORF25/BHQ3–cDNA18 duplex or
equal molar dosage of single-chain Cy5.5–MORF25 and were imaged.
Results The SPR studies showed that the immobilized cDNA18 rapidly captured the flowing MORF25 to provide a duplex with a slow dissociation
rate constant. Furthermore, when cMORF25 was next allowed to flow over the now immobilized duplex, the cDNA18 was unable to
prevent dissociation of the heteroduplex and the formation and release of the cMORF25-MORF25 homoduplex. Images of animals
obtained soon after receiving the Cy5.5–MORF25 singlet showed intense whole body fluorescence obscuring the target thigh.
However, only 5 minutes after receiving the Cy5.5–MORF25/BHQ3–cDNA18 duplex, the target thigh was clearly visible along with
only the kidneys.
Conclusions This first study of optical pretargeting provides a proof of concept that oligomer pretargeting found to be useful with radioactivity
detection is applicable with fluorescent detection as well. In addition, our results demonstrate that by using linear oligomers
for optical pretargeting, chain lengths (and base sequences) may be manipulated to provide duplexes with stabilities and fluorescence
inhibition optimized for pretargeting and other in vivo applications of optical imaging. 相似文献
937.
938.
Peter Y. Kim M.D. Bradley J. Monk M.D. Sanjay Chabra B.S. Robert A. Burger M.D. Steven A. Vasilev M.D. Alberto Manetta M.D. Philip J. DiSaia M.D. Michael L. Berman M.D. 《Gynecologic oncology》1998,69(3):243-247
Cervical carcinoma frequently metastasizes to the paraaortic region, necessitating extended field radiotherapy to effect a cure. As imaging modalities are unreliable in identifying all cases of paraaortic nodal metastases (PAN), surgical staging is often utilized prior to radiotherapy. This study was aimed at identifying factors predictive of survival in women with cervical carcinoma and paraaortic metastases. In particular, survival based on extent of paraaortic disease was examined. The study group consisted of 43 women (stages IB–IVB) identified between 1982 and 1993 who were treated with extended field radiation for cervical carcinoma with histologically confirmed paraaortic metastases. The estimated 5-year survival for the study population was 24% with a median survival of 18 months. Pelvic tumor size had a significant impact on survival with the median survival being 34 months if the primary lesion was <6 cm compared to 14 months if ≥6 cm (P= 0.01). Eight of the 26 (31%) women without residual PAN disease after surgical staging remain alive and disease free (mean follow-up, 74 months). In contrast, only 1 of the 17 (6%) women with gross residual PAN is alive 71 months after treatment (P= 0.05). However, a comparison of Kaplan–Meier survival curves did not show a statistically significant advantage to the surgical excision of grossly involved PAN (P= 0.98). Although long-term survival among women with grossly involved, unresected paraaortic metastases is uncommon, further study is necessary to elucidate the role of surgical excision of bulky aortic disease in women with cervical cancer. 相似文献
939.
A laparoscopic approach was used for penile revascularization in a patient with vasculogenic impotence to avoid the long abdominal incision which was traditionally required to harvest the inferior epigastric artery as a neoarterial source. Despite the time-consuming nature of laparoscopy, this procedure was as efficacious but less morbid and required less convalescence than open revascularization. Whether more patients may benefit from this procedure must be evaluated in further studies. 相似文献
940.
Childhood kidney tumors seldom metastasize into the cranial cavity unless it is a special histological variant. We report a 4-year-old boy with multiple intracranial metastases in the left parietotemporal and right cerebellar area from primary clear cell sarcoma of the kidney without evidence of bony metastases. Metastatic tumor revealed nests of uniformly polygonal cells with clear cytoplasm demarcated by delicate fibrovascular arcades. Tumor cells were positive for vimentin and negative for cytokeratin, S-100 protein, desmin, and myoglobin. Cellular proliferation rate measured by PCNA, and Ki-67 was not significantly different between primary tumor mass and metastatic brain lesion. Expression of p53 oncoprotein was not evident in both lesions. These findings suggested that the relapse and metastasis of clear cell sarcoma of the kidney was probably due to regrowth of micro-metastases which were present at an early stage of disease. 相似文献